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Sample records for metastatic ovarian tumor

  1. Expression profile of mucins in ovarian mucinous tumors: distinguishing primary ovarian from metastatic tumors.

    PubMed

    Wang, Jayson; El-Bahrawy, Mona A

    2014-03-01

    Ovarian mucinous tumors (OMTs) of the intestinal type share morphologic features with primary tumors of other sites, and it can often be difficult to distinguish primary ovarian from metastatic mucinous tumors. MUC1, MUC2, MUC5AC, and MUC6 expressions were studied by immunohistochemistry in 36 OMTs of intestinal type (17 malignant, 19 borderline), 18 pancreatic, 12 biliary, 15 esophageal, 9 gastric, and 7 colorectal/appendiceal adenocarcinomas. All samples were from primary sites, except for colorectal tumors which were from ovarian metastases. Borderline and malignant OMTs show similar mucin immunoprofile, being strongly and uniformly positive for MUC5AC (97.2% of cases), whereas only focally positive for MUC1 (19.4%), MUC2 (38.9%), and MUC6 (22.2%). The positive frequencies of pancreatic adenocarcinomas for MUC1, MUC2, MUC5AC, and MUC6, respectively, were 100%, 16.7%, 94.4%, and 61.1%; for biliary (cholangiocarcinomas) were 91.7%, 0%, 16.7%, and 8.3%; for esophageal carcinomas were 73.3%, 33.3%, 53.3%, and 26.7%; for gastric carcinomas were 44.4%, 44.4%, 44.4%, and 0% and for lower gastrointestinal tract cancers were 28.6%, 85.7%, 42.9%, and 0%. Our study shows that OMTs are usually MUC5AC+/MUC1-, which is different from pancreatic, biliary, esophageal, gastric, and colorectal/appendiceal carcinomas. We recommend that these mucin stains be added to the panel of immunostains to differentiate metastatic tumors to the ovary from primary OMTs. PMID:24487472

  2. Expression Profiling of Primary and Metastatic Ovarian Tumors Reveals Differences Indicative of Aggressive Disease

    PubMed Central

    Brodsky, Alexander S.; Fischer, Andrew; Miller, Daniel H.; Vang, Souriya; MacLaughlan, Shannon; Wu, Hsin-Ta; Yu, Jovian; Steinhoff, Margaret; Collins, Colin; Smith, Peter J. S.; Raphael, Benjamin J.; Brard, Laurent

    2014-01-01

    The behavior and genetics of serous epithelial ovarian cancer (EOC) metastasis, the form of the disease lethal to patients, is poorly understood. The unique properties of metastases are critical to understand to improve treatments of the disease that remains in patients after debulking surgery. We sought to identify the genetic and phenotypic landscape of metastatic progression of EOC to understand how metastases compare to primary tumors. DNA copy number and mRNA expression differences between matched primary human tumors and omental metastases, collected at the same time during debulking surgery before chemotherapy, were measured using microarrays. qPCR and immunohistochemistry validated findings. Pathway analysis of mRNA expression revealed metastatic cancer cells are more proliferative and less apoptotic than primary tumors, perhaps explaining the aggressive nature of these lesions. Most cases had copy number aberrations (CNAs) that differed between primary and metastatic tumors, but we did not detect CNAs that are recurrent across cases. A six gene expression signature distinguishes primary from metastatic tumors and predicts overall survival in independent datasets. The genetic differences between primary and metastatic tumors, yet common expression changes, suggest that the major clone in metastases is not the same as in primary tumors, but the cancer cells adapt to the omentum similarly. Together, these data highlight how ovarian tumors develop into a distinct, more aggressive metastatic state that should be considered for therapy development. PMID:24732363

  3. Metastatic brain tumor

    MedlinePlus

    Brain tumor - metastatic (secondary); Cancer - brain tumor (metastatic) ... For many people with metastatic brain tumors, the cancer is not curable. It will eventually spread to other areas of the body. Prognosis depends on the type of tumor ...

  4. Metastatic Malignant Ovarian Steroid Cell Tumor: A Case Report and Review of the Literature

    PubMed Central

    Lee, Jessica; John, Veena S.; Liang, Sharon X.; D'Agostino, Catherine A.; Menzin, Andrew W.

    2016-01-01

    We report a case of malignant ovarian steroid cell tumor not otherwise specified (NOS) in a 47-year-old female who presented with hirsutism, virilization, and amenorrhea. At the time of laparotomy, the tumor had already spread to the pelvic cul-de-sac. She underwent a total hysterectomy, bilateral salpingo-oophorectomy, and tumor resection with no residual disease. She received three cycles of bleomycin, etoposide, and cisplatin (BEP) and is now free of disease 24 months after surgery. Literature review of ovarian steroid cell tumors NOS including clinicopathological features and clinical management was performed. PMID:27375912

  5. PAX2, PAX8 and CDX2 Expression in Metastatic Mucinous, Primary Ovarian Mucinous and Seromucinous Tumors and Review of the Literature.

    PubMed

    Ates Ozdemir, D; Usubutun, A

    2016-07-01

    Ovarian cancer is the most common cause of gynecologic cancer death. Both morphologically and immunohistochemically, metastatic mucinous tumors are the best mimickers of mucinous ovarian tumors; its pathogenesis still remains a mystery. PAX2 and PAX8 immunohisyochemistries are useful for differentiating numerous primary tumour types from metastatic ones. There are few studies in literature about PAX expressions in mucinous and seromucinous tumors. None of these are takes into account the histologic type (whether it is seromucinous or mucinous) or the metastatic origin. With this purpose hematoxylin and eosine slides of ovarian mucinous and seromucinous tumors were re-evaluated and one block was chosen for each case. The study included 76 ovarian mucinous and seromucinous tumors of the ovary reported in Hacettepe University department of pathology between 2000 and 2013. Tissue microarray (TMA) was designed from the chosen blocks, PAX2, PAX8, CDX2 immunostains was preformed to the TMA slides. As a result, most of the metastatic cases were negative for PAX2 (91.2 %) and PAX8 (86.3 %), many were diffusely and strongly positive for CDX2 (68.2 %). Seromucinous tumors were devoid of CDX2 expression; but all cases (except one) displayed strong and diffuse positivity with PAX8. In other words differing from mucinous tumors, seromucinous tumors show strong PAX8 positivity-similar to serous tumors. This study shows that PAX8 and CDX2 could be useful in differentiating primary mucinous from metastatic tumor. Furthermore unlike the homogeneity in seromucinous tumors for PAX8 and CDX2 mucinous tumors shows heterogeneity with different expression patterns. PMID:26797858

  6. Inflammatory Breast Cancer from Metastatic Ovarian Cancer

    PubMed Central

    Achariyapota, Vuthinun; Chuangsuwanich, Tuenjai

    2016-01-01

    Metastases to the breast from tumors other than breast carcinomas are extremely rare and represent only 0.2–1.3% of all diagnosed malignant breast tumors. Furthermore, while the most common sites for advanced ovarian cancer metastases are the liver, lung, and pleura, metastasis to the breast from a primary ovarian cancer is uncommon and has only been reported in 0.03–0.6% of all breast cancers. Here we describe a case report of a 50-year-old female patient with a rare case of breast metastases from an advanced ovarian cancer, presenting as inflammatory breast cancer. Our observations emphasize the clinical importance of distinguishing between primary and metastatic breast cancer during diagnosis for the purpose of appropriate prognosis and treatment. PMID:27047697

  7. Metastatic brain tumor

    MedlinePlus

    ... brain from an unknown location. This is called cancer of unknown primary (CUP) origin. Growing brain tumors can place pressure ... not know the original location. This is called cancer of unknown primary (CUP) origin. Metastatic brain tumors occur in about ...

  8. Metastatic pleural tumor

    MedlinePlus

    ... persons. Alternative Names Tumor - metastatic pleural Images Pleural space References Arenberg D, Pickens A. Metastatic malignant tumors. In: Mason RJ, Murray JF, Broaddus VC, et al., eds. Murray and Nadel's Textbook of Respiratory Medicine . 5th ed. Philadelphia, PA: Elsevier Saunders; 2010:chap ...

  9. Ovarian tumors secreting insulin.

    PubMed

    Battocchio, Marialberta; Zatelli, Maria Chiara; Chiarelli, Silvia; Trento, Mariangela; Ambrosio, Maria Rosaria; Pasquali, Claudio; De Carlo, Eugenio; Dassie, Francesca; Mioni, Roberto; Rebellato, Andrea; Fallo, Francesco; Degli Uberti, Ettore; Martini, Chiara; Vettor, Roberto; Maffei, Pietro

    2015-08-01

    Combined ovarian germ cell and neuroendocrine tumors are rare. Only few cases of hyperinsulinism due to ovarian ectopic secretion have been hypothesized in the literature. An ovarian tumor was diagnosed in a 76-year-old woman, referred to our department for recurrent hypoglycemia with hyperinsulinism. In vivo tests, in particular fasting test, rapid calcium infusion test, and Octreotide test were performed. Ectopic hyperinsulinemic hypoglycemia was demonstrated in vivo and hypoglycemia disappeared after hysteroadnexectomy. Histological exam revealed an ovarian germ cell tumor with neuroendocrine and Yolk sac differentiation, while immunostaining showed insulin positivity in neuroendocrine cells. A cell culture was obtained by tumoral cells, testing Everolimus, and Pasireotide. Insulin was detected in cell culture medium and Everolimus and Pasireotide demonstrated their potentiality in reducing insulin secretion, more than controlling cell viability. Nine cases of hyperinsulinism due to ovarian ectopic secretion reported in literature have been reviewed. These data confirm the ovarian tissue potentiality to induce hyperinsulinemic hypoglycemic syndrome after neoplastic transformation. PMID:25896552

  10. The Use of Lattice Radiation Therapy (LRT) in the Treatment of Bulky Tumors: A Case Report of a Large Metastatic Mixed Mullerian Ovarian Tumor

    PubMed Central

    Amendola, Beatriz E; Perez, Naipy; Amendola, Marco; Wu, Xiaodong

    2015-01-01

    The objective of this teaching case is to report the excellent results of using lattice radiation therapy (LTR) for the treatment of a large metastasis from ovarian carcinosarcoma. This new technical concept extrapolates the traditional spatially fractionated radiation therapy (GRID) technique to advanced three-dimensional (3D) high-dose radiation therapy using modern instrumentation in radiation oncology. We report a case of a 61-year-old female with a large metastatic mass from ovarian carcinosarcoma treated by this procedure with excellent clinical and image-based follow-up results for more than four years. PMID:26719832

  11. Intraperitoneal delivery of paclitaxel by poly(ether-anhydride) microspheres effectively suppresses tumor growth in a murine metastatic ovarian cancer model

    PubMed Central

    Yang, Ming; Yu, Tao; Wood, Joseph; Wang, Ying-Ying; Tang, Benjamin C.; Zeng, Qi; Simons, Brian W.; Fu, Jie; Chuang, Chi-Mu; Lai, Samuel K.; Wu, T.-C.; Hung, Chien-Fu; Hanes, Justin

    2014-01-01

    Intraperitoneal (IP) chemotherapy is more effective than systemic chemotherapy for treating advanced ovarian cancer, but is typically associated with severe complications due to high dose, frequent administration schedule, and use of non-biocompatible excipients/delivery vehicles. Here, we developed paclitaxel (PTX)-loaded microspheres composed of di-block copolymers of poly(ethylene glycol) and poly(sebacic acid) (PEG-PSA) for safe and sustained IP chemotherapy. PEG-PSA microspheres provided efficient loading (~ 13% w/w) and prolonged release (~ 13 days) of PTX. In a murine ovarian cancer model, a single dose of IP PTX/PEG-PSA particles effectively suppressed tumor growth for more than 40 days and extended the median survival time to 75 days compared to treatments with Taxol® (47 days) or IP placebo particles (34 days). IP PTX/PEG-PSA was well tolerated, with only minimal to mild inflammation. Our findings support PTX/PEG–PSA microspheres as a promising drug delivery platform for IP therapy of ovarian cancer, and potentially other metastatic peritoneal cancers. PMID:24816829

  12. Talazoparib and HSP90 Inhibitor AT13387 in Treating Patients With Metastatic Advanced Solid Tumor or Recurrent Ovarian, Fallopian Tube, Primary Peritoneal, or Triple Negative Breast Cancer

    ClinicalTrials.gov

    2016-07-22

    Adult Solid Neoplasm; Estrogen Receptor Negative; Fallopian Tube Serous Neoplasm; HER2/Neu Negative; Ovarian Serous Adenocarcinoma; Ovarian Serous Tumor; Primary Peritoneal Serous Adenocarcinoma; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Triple-Negative Breast Carcinoma

  13. [Metastatic tumors in the ovary, difficulties of histologic diagnosis].

    PubMed

    Tamás, Judit; Vereczkey, Ildikó; Tóth, Erika

    2015-09-01

    The ovary is a common site of metastases. Secondary tumors account for 3-40% of all ovarian malignancies. Most ovarian metastases arise from the colon, although tumors of the breast, stomach and endometrium are also common places of origin. Clinical and histological features of metastatic tumors frequently mimic primary ovarian malignancies, causing serious diagnostic problems for the surgical pathologist. However, differentiation between primary ovarian cancer and ovarian metastasis is important in order to prevent inappropriate management and suboptimal treatment. The distinction between primary and secondary ovarian malignancies is especially difficult in cases when the metastasis is diagnosed before the primary tumor. Frozen section is widely used in the intra-operative assessment of patients with ovarian tumors but it can be very difficult to distinguish certain types of primary ovarian tumors and metastases from other sites. We examined 152 cases of secondary ovarian neoplasm diagnosed at the National Institute of Oncology, Hungary from 2000 to 2014. Colorectal cancer was the most common primary tumor (58 cases), followed by breast (33 cases), endometrium (30 cases) and stomach cancer (13 cases). The differential diagnosis proved the most difficult in cases when endometrioid and mucinous tumors were present in the ovaries. Metastases of colorectal and gastric adenocarcinomas may simulate benign or borderline cystadenomas too. In these cases the knowledge of the patient's history and immunohistochemical stains were helpful. In our study we discuss the diagnostic challenge of distinguishing these secondary ovarian tumors from primary ovarian neoplasms and the limits of the intraoperative frozen sections. PMID:26339910

  14. [Morphology of secondary ovarian tumors and metastases].

    PubMed

    Horn, L-C; Einenkel, J; Handzel, R; Höhn, A K

    2014-07-01

    The distinction between primary and secondary (metastatic) ovarian tumors is essential for the selection of appropriate surgical interventions, chemotherapeutic treatment and prognostic evaluation for the patient. Metastatic tumors of the ovary range between 5 % and 30 %. The majority of ovarian metastases in Europe and North America derive from colorectal (25-50 %) and breast cancers (8-25 %). A major issue is the differential diagnosis of mucinous tumors. Major features favoring metastasis include bilaterality, size < 10 cm, ovarian surface involvement, extensive intra-abdominal spread, and infiltrative growth within the ovary involving the corpus albicans and corpora lutea. An algorithm using bilaterality and tumor size (cut-off 10 cm) allows correct categorization in approximately  85 % of the cases. Although immunohistochemistry (especially CK7 and CK20 in mucinous tumors) using a panel of antibodies plays a valuable role and is paramount in the diagnosis, the results must be interpreted with caution and within the relevant clinical and histopathological context. It is necessary to note that the correct diagnosis of ovarian metastases always needs interdisciplinary and multidisciplinary approaches. PMID:24859239

  15. An evaluation of the morphologic features of low-grade mucinous neoplasms of the appendix metastatic in the ovary, and comparison with primary ovarian mucinous tumors.

    PubMed

    Stewart, Colin J R; Ardakani, Nima M; Doherty, Dorota A; Young, Robert H

    2014-01-01

    It may be difficult to distinguish ovarian involvement by a low-grade appendiceal mucinous neoplasm (LAMN) from a primary gastrointestinal-type primary borderline (proliferative) ovarian tumor (IBMT) or an ovarian mucinous tumor arising within a teratoma, particularly when the latter is associated with mucinous ascites/pseudomyxoma peritonei. We noted that LAMNs involving the ovaries show 2 distinctive histologic features, "scalloped" glands and subepthelial stromal clefts, whereas IBMTs more often are associated with reactive cellular stroma and histiocyte aggregates (mucin granulomas). The frequency of these features was investigated in 18 LAMNs (16 with pseudomyxoma peritonei), 18 primary IBMTs, and 6 teratoma-associated mucinous tumors (selected on the basis of associated pseudomyxoma peritonei). Scalloped glands and subepithelial clefts were identified in 17 and 16 LAMNs, respectively, and in 3 and 7 IBMTs, respectively. Conversely, reactive stroma and histiocyte aggregates were present in 2 and 0 LAMNs, respectively, and in 11 and 10 IBMTs, respectively. LAMNs were often bilateral (12/18 cases) and they more frequently showed mucin dissection of the ovarian stroma and tall mucin-rich (hypermucinous) epithelial cells compared with IBMTs. Our findings suggest that scalloped glands, subepithelial clefts, cellular stroma, and histiocyte aggregates may be useful additional morphologic parameters to help distinguish these tumor types. However, teratoma-associated mucinous neoplasms can show identical histologic features to those of LAMNs involving the ovary, and therefore accurate diagnosis of such cases requires careful macroscopic and microscopic examinations of the ovaries together with complete histologic assessment of the appendix. PMID:24300528

  16. Ruptured metastatic ovarian carcinoma presenting as acute abdomen.

    PubMed

    Linn, J J; Yen, C C; Wang, P H; Yen, M S; Chao, K C; Yuan, C C; Ng, H T

    2000-03-01

    Acute abdomen is a challenge to first-line physicians because of frequently missed diagnoses and potential follow-on legal problems. Improving the management of these patients is of paramount importance, not only for saving lives, but also for reducing untoward problems associated with improper management. We present a case of a patient with acute abdomen due to intraperitoneal hemorrhage secondary to rupture of an ovarian tumor. Following emergency surgery, the patient was diagnosed with metastatic ovarian carcinoma. Because of improper preparation of the gastrointestinal tract, the patient underwent repeat exploratory laparotomy for colon carcinoma. Although this situation did not affect the outcome of the patient in this case, we are concerned that the patient did not benefit from a single operation, with primary complete excision of the tumor plus a colostomy. The outcome of patients with pelvic malignancy, especially those with ovarian carcinoma, might be better if initial surgery achieved optimal tumor debulking. This is possible with good preoperative planning and preparation. We emphasize the importance of preoperative preparation in spite of urgently needed care. Furthermore, every first-line physician should communicate the possibility of malignancy to patients and their families. PMID:10746423

  17. Ovarian tumors of the hen.

    PubMed Central

    Fredrickson, T N

    1987-01-01

    Present available information regarding ovarian tumors in hens is incomplete in most aspects, and this lack of knowledge hampers use of hens as models for study of ovarian cancer. A study of 466 hens ranging from 2 to 7 years of age and covering a period of more than 3 years has provided much needed information relative to reproductive tract neoplasia. On the basis of this study, it is apparent that hens have a high rate of ovarian tumors, but that such tumors are uncommon in hens less than 2 years of age. Adenocarcinomas with a high degree of morphologic variability are the most common ovarian tumors in hens. Hormonal imbalance does not appear to be a factor in the development of these adenocarcinomas. Steroidogenic and morphologically distinctive granulosa cell tumors originating from follicles in atrophic ovaries represent another common ovarian tumor type. Unique to the hen are oviductal adenocarcinomas. These tumors arise from the albumin-secreting glands of the oviduct, occur with relatively high frequency, and must be differentiated from ovarian adenocarcinomas. Images PLATE 1. PLATE 2. PLATE 3. PLATE 4. PLATE 5. PLATE 6. PLATE 7. PLATE 8. PLATE 9. PLATE 10. PLATE 11. PLATE 12. PLATE 13. PLATE 14. PLATE 15. PLATE 16. PLATE 17. PLATE 18. PLATE 19. PLATE 20. PLATE 21. PLATE 22. PLATE 23. PLATE 24. PLATE 25. PMID:3665870

  18. Retropancreatic Ovarian Tumor.

    PubMed

    Acharya, Soumyo Ranjan; Dasgupta, Prosenjit; Das, Subhobroto; Halder, Sandip; Panda, Nilanjan

    2016-06-01

    Retroperitoneal mucinous cystadenomas are rare lesions (less than 50 reported) characterized by presence of ovary like stroma of unknown origin. However, germinal component of ovary has never been found in them. The pancreas occasionally gives rise to mucinous cystadenomas, but they are always intrapancreatic. We report a unique case of a rare retroperitoneal mucinous cystadenomas with presence of ovarian follicles in a 45-year-old lady who presented with an abdominal mass. This was successfully excised. Though retroperitoneal mucinous cystadenomas are rare, presence of ovarian follicle (germ cell) in them has never been reported before. PMID:27358520

  19. Adrenalectomy for metastatic adrenal tumors.

    PubMed

    Kita, Masafumi; Tamaki, Gaku; Okuyama, Mitsuhiko; Saga, Yuji; Kakizaki, Hidehiro

    2007-11-01

    The indications for adrenalectomy in cases of metastatic adrenal tumor remain controversial. To clarify indications and outcomes of adrenalectomy for adrenal metastasis, we performed a retrospective review of all 8 patients who underwent adrenalectomy for adrenal metastasis between 1990 and 2006 in Asahikawa Medical College Hospital. The Primary tumor was renal cell carcinoma in 2 cases, and eccrine poro carcinoma, rectal cancer, lung cancer, melanoma, bladder cancer and cancer of unknown origin in 1 case each. Open adrenalectomy was performed in all cases, including 1 case that was converted from laparoscopic adrenalectomy. Of the 4 patients with solitary adrenal metastasis, 3 were considered tumor-free after adrenalectomy, while the remaining patient was not due to unresectable primary tumor. Of the 3 patients with complete resection, one remained alive as of 88 months after adrenalectomy but was then lost to follow-up, and the other 2 patients remain alive 12 and 7 months after adrenalectomy. Of the 2 patients with other resectable metastasis who were tumor-free after removal of all metastases, one was alive 31 months postoperatively and the other died 23 months after operation. The remaining 2 cases with other unresectable metastasis died within 6 months after adrenalectomy. At least in cases of solitary adrenal metastasis, adrenalectomy can be effective if other valid methods are unavailable. PMID:18051798

  20. Expression of REG4 in ovarian mucinous tumors.

    PubMed

    Huang, Qiong; Chen, Xiaoduan; Lu, Weiguo; Lai, Maode; Lu, Bingjian

    2014-04-01

    Regenerating islet-deprived gene family, number 4 (REG4), is a novel marker for intestinal differentiation. We performed immunohistochemical studies on REG4, cytokeratin (CK)7, CK20, and caudal type homeobox 2 (CDX2) in 291 ovarian mucinous tumors. There were 226 primary tumors and 65 metastatic tumors. The primary tumors comprised 69/226 mucinous cystadenomas, 79/226 mucinous borderline tumors (64/79 intestinal-type and 15/79 endocervical-like tumors), and 78/226 mucinous carcinomas. We found that REG4 expression was significantly higher in mucinous borderline tumors (30/79, 38.0%) and primary mucinous carcinomas (26/78, 33.3%) than in mucinous cystadenomas (4/69, 5.8%; P<0.05). However, REG4 expression was more commonly associated with intestinal-type, borderline, mucinous tumors rather than the endocervical-like type (30/64 vs. 0/15, P<0.001). There was a significant correlation between the REG4 and CDX2 expression profiles in primary ovarian mucinous tumors (r=0.772, P<0.001). REG4, CDX2, and diffuse CK20 had higher expression frequencies in metastatic lower gastrointestinal adenocarcinoma than in primary mucinous tumors (P<0.01). The CK7/REG4 coordinate expression profile was comparable in diagnostic value to CK7/CK20 or CK7/CDX2 profile. We conclude that REG4 expression is common in mucinous borderline tumors of the intestinal type as it is absent in the endocervical-like form in this series. Expression of CK7/REG4 may contribute to the differential diagnosis between primary and metastatic ovarian mucinous tumors. PMID:23958547

  1. Sorafenib Tosylate in Treating Patients With Progressive Metastatic Neuroendocrine Tumors

    ClinicalTrials.gov

    2014-11-14

    Gastrinoma; Glucagonoma; Insulinoma; Metastatic Gastrointestinal Carcinoid Tumor; Neuroendocrine Tumor; Pancreatic Polypeptide Tumor; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Islet Cell Carcinoma; Somatostatinoma; WDHA Syndrome

  2. Regorafenib in Treating Patients With Advanced or Metastatic Neuroendocrine Tumors

    ClinicalTrials.gov

    2015-08-29

    Gastrinoma; Glucagonoma; Insulinoma; Metastatic Gastrointestinal Carcinoid Tumor; Pancreatic Polypeptide Tumor; Pulmonary Carcinoid Tumor; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Islet Cell Carcinoma; Somatostatinoma

  3. General Information about Ovarian Germ Cell Tumors

    MedlinePlus

    ... Germ Cell Tumors Treatment (PDQ®)–Patient Version General Information About Ovarian Germ Cell Tumors Go to Health ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  4. Temsirolimus and Vinorelbine Ditartrate in Treating Patients With Unresectable or Metastatic Solid Tumors

    ClinicalTrials.gov

    2016-06-09

    Extensive Stage Small Cell Lung Cancer; Hereditary Paraganglioma; Male Breast Cancer; Malignant Paraganglioma; Metastatic Gastrointestinal Carcinoid Tumor; Metastatic Pheochromocytoma; Pancreatic Polypeptide Tumor; Recurrent Breast Cancer; Recurrent Cervical Cancer; Recurrent Endometrial Carcinoma; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Islet Cell Carcinoma; Recurrent Neuroendocrine Carcinoma of the Skin; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pheochromocytoma; Recurrent Prostate Cancer; Recurrent Renal Cell Cancer; Recurrent Small Cell Lung Cancer; Recurrent Uterine Sarcoma; Regional Gastrointestinal Carcinoid Tumor; Regional Pheochromocytoma; Stage III Cervical Cancer; Stage III Endometrial Carcinoma; Stage III Neuroendocrine Carcinoma of the Skin; Stage III Ovarian Epithelial Cancer; Stage III Ovarian Germ Cell Tumor; Stage III Prostate Cancer; Stage III Renal Cell Cancer; Stage III Uterine Sarcoma; Stage IIIA Breast Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Breast Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Stage IV Endometrial Carcinoma; Stage IV Neuroendocrine Carcinoma of the Skin; Stage IV Non-small Cell Lung Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Prostate Cancer; Stage IV Renal Cell Cancer; Stage IV Uterine Sarcoma; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer; Thyroid Gland Medullary Carcinoma

  5. [Presumed benign ovarian tumors during pregnancy].

    PubMed

    Tariel, O; Huissoud, C; Rudigoz, R C; Dubernard, G

    2013-12-01

    The incidence of ovarian tumors diagnosed during pregnancy is between 0.3 and 5.4% (LE2). The most common ovarian tumors diagnosed during pregnancy are functional cysts diagnosed incidentally during the first trimester ultrasound (LE2) and spontaneous regression is often observed. Dermoid cysts and cystadenoma are the most frequent organic benign ovarian tumors diagnosed during pregnancy (LE2). The main complication of presumed benign ovarian tumor (PBOT) during pregnancy is adnexal torsion and is estimated at around 8% (LE2), especially at the end of the first trimester and during the second trimester (LE4). Tumor markers are not reliable during pregnancy to assess the risk of malignancy of ovarian tumor (LE2). Ultrasound remains the gold standard for characterizing an ovarian tumor during pregnancy (LE3), but with a lower specificity for the diagnosis of malignancy. Pelvic MRI is accurate in the diagnosis of ovarian tumors during pregnancy and brings additional information to ultrasound (LE4). Ultrasound-guided aspiration of ovarian tumors is not recommended during pregnancy (grade C). Expectation is recommended in cases of PBOT during pregnancy, which does not enlarge (grade C). Whatever the gestational age, surgery is recommended in patients with symptoms suggesting an adnexal torsion (grade C). Laparoscopy is possible during the first and second trimester of pregnancy for the management of symptomatic PBOT (LE3). The risk of miscarriage following surgery (laparoscopy and laparotomy) for ovarian tumor during pregnancy is estimated at 2.8% (LE3). The route of delivery should not be modified by the ovarian tumour, except in case of praevia cyst requiring a cesarean section, a complication or suspicion of malignancy (grade C). Surgical treatment of PBOT may be performed during a cesarean section indicated for another reason. The risk of torsion is increased during the postpartum period (LE4). PMID:24210242

  6. Gefitinib in Treating Patients With Progressive Metastatic Neuroendocrine Tumors

    ClinicalTrials.gov

    2013-06-03

    Gastrinoma; Glucagonoma; Insulinoma; Metastatic Gastrointestinal Carcinoid Tumor; Pancreatic Polypeptide Tumor; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Islet Cell Carcinoma; Somatostatinoma; WDHA Syndrome

  7. SATB2 Expression Distinguishes Ovarian Metastases of Colorectal and Appendiceal Origin From Primary Ovarian Tumors of Mucinous or Endometrioid Type.

    PubMed

    Moh, Michelle; Krings, Gregor; Ates, Deniz; Aysal, Anil; Kim, Grace E; Rabban, Joseph T

    2016-03-01

    The primary origin of some ovarian mucinous tumors may be challenging to determine, because some metastases of extraovarian origin may exhibit gross, microscopic, and immunohistochemical features that are shared by some primary ovarian mucinous tumors. Metastases of primary colorectal, appendiceal, gastric, pancreatic, and endocervical adenocarcinomas may simulate primary ovarian mucinous cystadenoma, mucinous borderline tumor, or mucinous adenocarcinoma. Recently, immunohistochemical expression of SATB2, a transcriptional regulator involved in osteoblastic and neuronal differentiation, has been shown to be a highly sensitive marker of normal colorectal epithelium and of colorectal adenocarcinoma. SATB2 expression has not been reported in normal epithelium of the female reproductive tract. Therefore, we hypothesized that SATB2 may be of value in distinguishing ovarian metastases of colorectal adenocarcinoma from primary ovarian mucinous tumors and from primary ovarian endometrioid tumors. Among primary ovarian tumors, SATB2 staining was observed in 0/22 mucinous cystadenomas that lacked a component of mature teratoma, 4/12 mucinous cystadenomas with mature teratoma, 1/60 mucinous borderline tumors, 0/17 mucinous adenocarcinomas, 0/3 endometrioid borderline tumors, and 0/72 endometrioid adenocarcinomas. Among ovarian metastases, SATB2 staining was observed in 24/32 (75%) colorectal adenocarcinomas; 8/10 (80%) low-grade appendiceal mucinous neoplasms; and 4/4 (100%) high-grade appendiceal adenocarcinomas. No SATB2 staining was observed in any ovarian metastasis of pancreatic, gastric, gallbladder, or endocervical origin. Evaluation of primary extraovarian tumors showed the highest incidences of SATB2 staining among primary colorectal adenocarcinomas (71%), primary appendiceal low-grade mucinous neoplasms (100%), and primary appendiceal high-grade adenocarcinomas (100%). Similar to their metastatic counterparts, none of the primary pancreatic or gastric

  8. [Ovarian germ cell tumors in girls].

    PubMed

    Nechushkina, I V; Karseladze, A I

    2015-01-01

    Morphological structure of tumor influences on the clinical course of the disease in children with germ cell tumors. Patients with ovarian dysgerminoma at the time of diagnosis are significantly older than patients with immature teratoma and yolk sac tumor. Immature teratoma and mixed germ cell tumors are significantly larger compared to other germ cell tumors. Yolk sac tumor and embryonal carcinoma are the most common cause of emergency surgical interventions and are accompanied by rupture of tumor capsule. PMID:26087605

  9. Serous Ovarian Carcinoma Recurring as Malignant Mixed Mullerian Tumor

    PubMed Central

    Hale, Demir; Senem, Demiroz Ahu; Ovgu, Aydin; Hakan, Erenel; Sennur, Ilvan; Zerrin, Calay; Fuat, Demirkiran

    2015-01-01

    Only five cases of recurrence of malignant mixed Mullerian tumor (carcinosarcoma) from the ovarian carcinoma have been published in the literature to our knowledge. A 64-year-old woman first underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy because of pelvic mass. Histological diagnosis was serous papillary carcinoma of the left ovary. After six courses of chemotherapy, CA125 level returned to normal range. However, she had persistent multiple mediastinal and para-aortic lymphadenopathies in spite of additional six courses of chemotherapy. Then she underwent the second operation about 2 years after primary surgery. Multiple excisional biopsies were taken from subcutaneous tissue, over the bowels and the left external iliac artery. The histopathological diagnosis which was confirmed by immunohistochemical study was malignant mixed Mullerian tumor for all metastatic foci. A rare case of ovarian serous papillary carcinoma recurring as malignant mixed Mullerian tumor is reported. PMID:26713165

  10. Mucinous borderline ovarian tumor with ascites.

    PubMed

    Batool, Tahira; Ullah, Nasreen Rehmat

    2014-11-01

    Borderline mucinous tumors are epithelial ovarian tumors with low rate of growth and low potential to invade or metastasize and associated with significantly better prognosis and excellent disease-free survival after surgical removal than other epithelial ovarian cancers. The accepted initial treatment is surgical removal of the tumor. Fertility-sparing surgery may suffice in young patients with tumors confined to the ovary. Radical surgery is recommended in patients with advanced disease and advanced age. Long-term surveillance is recommended to document and treat late recurrences. We report a case of a 59 years old postmenopausal patient with complex ovarian mucinous tumor and gross ascites; she had received three lines of chemotherapeutic agents pre-operatively, without any favorable outcome. Then, she went for staging laparotomy and histopathology showed borderline ovarian mucinous tumor required no further treatment and is fine till date. PMID:25518783

  11. TUMOR PENETRATING MICROPARTICLES FOR INTRAPERITONEAL THERAPY OF OVARIAN CANCER

    PubMed Central

    Lu, Ze; Tsai, Max; Lu, Dan; Wang, Jie; Wientjes, M. Guillaume; Au, Jessie L.-S.

    2009-01-01

    Intraperitoneal (IP) chemotherapy prolongs survival of ovarian cancer patients, but its utility is limited by treatment-related complications and inadequate drug penetration in larger tumors. Previous IP therapy used the paclitaxel/Cremophor formulation designed for intravenous use. The present report describes the development of paclitaxel-loaded microparticles designed for IP treatment (referred to as tumor penetrating microparticles or TPM). Evaluation of TPM was performed using IP metastatic, human ovarian SKOV3 xenograft tumor models in mice. TPM were retained in the peritoneal cavity and adhered to tumor surface. TPM consisted of two biocompatible and biodegradable polymeric components with different drug release rates; one component released the drug load rapidly to induce tumor priming while the second component provided sustained drug release. Tumor priming, by expanding interstitial space, promoted transport and penetration of particulates in tumors. These combined features resulted in the following advantages over paclitaxel/Cremophor: greater tumor targeting (16-times higher and more sustained concentration in omental tumors), lower toxicity to intestinal crypts and less body weight loss, greater therapeutic efficacy (longer survival and higher cure rate), and greater convenience (less frequent dosing). TPM may overcome the toxicities and compliance-related problems that have limited the utility of IP therapy. PMID:18780831

  12. Novel Treatment Shrinks Ovarian Tumors in Mice

    Cancer.gov

    Researchers have developed a new approach for treating tumors that express mutant versions of the p53 protein, which are present in more than half of all cancers, including an aggressive and common subtype of ovarian cancer.

  13. Expression of serum amyloid a in human ovarian epithelial tumors: implication for a role in ovarian tumorigenesis.

    PubMed

    Urieli-Shoval, Simcha; Finci-Yeheskel, Zvezdana; Dishon, Shira; Galinsky, Daliah; Linke, Reinhold P; Ariel, Ilana; Levin, Mark; Ben-Shachar, Inbar; Prus, Diana

    2010-11-01

    Serum amyloid A (SAA) is an acute phase protein which is expressed primarily in the liver as a part of the systemic response to various injuries and inflammatory stimuli; its expression in ovarian tumors has not been described. Here, we investigated the expression of SAA in human benign and malignant ovarian epithelial tumors. Non-radioactive in situ hybridization applied on ovarian paraffin tissue sections revealed mostly negative SAA mRNA expression in normal surface epithelium. Expression was increased gradually as epithelial cells progressed through benign and borderline adenomas to primary and metastatic adenocarcinomas. Similar expression pattern of the SAA protein was observed by immunohistochemical staining. RT-PCR analysis confirmed the overexpression of the SAA1 and SAA4 genes in ovarian carcinomas compared with normal ovarian tissues. In addition, strong expression of SAA mRNA and protein was found in the ovarian carcinoma cell line OVCAR-3. Finally, patients with ovarian carcinoma had high SAA serum levels, which strongly correlated with high levels of CA-125 and C-reactive protein. Enhanced expression of SAA in ovarian carcinomas may play a role in ovarian tumorigenesis and may have therapeutic application. PMID:20713982

  14. Obesity Contributes to Ovarian Cancer Metastatic Success through Increased Lipogenesis, Enhanced Vascularity, and Decreased Infiltration of M1 Macrophages.

    PubMed

    Liu, Yueying; Metzinger, Matthew N; Lewellen, Kyle A; Cripps, Stephanie N; Carey, Kyle D; Harper, Elizabeth I; Shi, Zonggao; Tarwater, Laura; Grisoli, Annie; Lee, Eric; Slusarz, Ania; Yang, Jing; Loughran, Elizabeth A; Conley, Kaitlyn; Johnson, Jeff J; Klymenko, Yuliya; Bruney, Lana; Liang, Zhong; Dovichi, Norman J; Cheatham, Bentley; Leevy, W Matthew; Stack, M Sharon

    2015-12-01

    Epithelial ovarian cancer (EOC) is the leading cause of death from gynecologic malignancy, with high mortality attributable to widespread intraperitoneal metastases. Recent meta-analyses report an association between obesity, ovarian cancer incidence, and ovarian cancer survival, but the effect of obesity on metastasis has not been evaluated. The objective of this study was to use an integrative approach combining in vitro, ex vivo, and in vivo studies to test the hypothesis that obesity contributes to ovarian cancer metastatic success. Initial in vitro studies using three-dimensional mesomimetic cultures showed enhanced cell-cell adhesion to the lipid-loaded mesothelium. Furthermore, in an ex vivo colonization assay, ovarian cancer cells exhibited increased adhesion to mesothelial explants excised from mice modeling diet-induced obesity (DIO), in which they were fed a "Western" diet. Examination of mesothelial ultrastructure revealed a substantial increase in the density of microvilli in DIO mice. Moreover, enhanced intraperitoneal tumor burden was observed in overweight or obese animals in three distinct in vivo models. Further histologic analyses suggested that alterations in lipid regulatory factors, enhanced vascularity, and decreased M1/M2 macrophage ratios may account for the enhanced tumorigenicity. Together, these findings show that obesity potently affects ovarian cancer metastatic success, which likely contributes to the negative correlation between obesity and ovarian cancer survival. PMID:26573796

  15. Malignant metastatic carcinoid presenting as brain tumor

    PubMed Central

    Sundar, I. Vijay; Jain, S. K.; Kurmi, Dhrubajyoti; Sharma, Rakesh; Chopra, Sanjeev; Singhvi, Shashi

    2016-01-01

    Carcinoid tumors are rarely known to metastasise to the brain. It is even more rare for such patients to present with symptoms related to metastases as the initial and only symptom. We present a case of a 60-year-old man who presented with hemiparesis and imaging features suggestive of brain tumor. He underwent surgery and the histopathology revealed metastatic malignant lesion of neuroendocrine origin. A subsequent work up for the primary was negative. Patient was treated with adjuvant radiotherapy. We present this case to highlight the pathophysiological features, workup and treatment options of this rare disease and discuss the methods of differentiating it from more common brain tumors. PMID:27366273

  16. Malignant metastatic carcinoid presenting as brain tumor.

    PubMed

    Sundar, I Vijay; Jain, S K; Kurmi, Dhrubajyoti; Sharma, Rakesh; Chopra, Sanjeev; Singhvi, Shashi

    2016-01-01

    Carcinoid tumors are rarely known to metastasise to the brain. It is even more rare for such patients to present with symptoms related to metastases as the initial and only symptom. We present a case of a 60-year-old man who presented with hemiparesis and imaging features suggestive of brain tumor. He underwent surgery and the histopathology revealed metastatic malignant lesion of neuroendocrine origin. A subsequent work up for the primary was negative. Patient was treated with adjuvant radiotherapy. We present this case to highlight the pathophysiological features, workup and treatment options of this rare disease and discuss the methods of differentiating it from more common brain tumors. PMID:27366273

  17. Therapy for metastatic pancreatic neuroendocrine tumors

    PubMed Central

    Massironi, Sara; Conte, Dario; Peracchi, Maddalena

    2014-01-01

    Background Pancreatic neuroendocrine tumors (pNETs) are frequently malignant (50-80%, except for insulinoma) and may show an aggressive course with metastases to the liver as well as more distant sites. These heterogeneous neoplasms include functioning tumors, which secrete a variety of peptide hormones, and non-functioning tumors (up to 90% of pNETs), which often show metastases at the time of diagnosis. Methods A PubMed search was performed for English-language publications from 1995 through December 2012. Reference lists from studies selected were manually searched to identify further relevant reports. Manuscripts comparing different therapeutic options and advances for metastatic pNETs were selected. Results The therapeutic options for metastatic pNETs are expanding and include surgery, which remains the only curative approach, liver-directed therapies, and medical therapy. In selected cases also liver transplantation (OLT) may be considered. The option of OLT for metastatic disease is unique to neuroendocrine tumors. Recently, novel promising targeted therapies have been proposed for progressive well-differentiated pNETs. Conclusions The best therapeutic approach for pNETs is still matter of debating. However, since pNETs often show a more indolent behavior compared to other malignancies, the preservation of the quality of life of the patient and the personalization of the therapy according to tumor’s and patient’s features are mandatory. PMID:25332984

  18. Metastatic tumors of the oral cavity.

    PubMed

    Rao, Roopa S; Patil, Shankargouda; Sanketh, Ds; Amrutha, N

    2014-01-01

    The pivotal reason for morbidity and mortality of any type of cancer is due to metastasis that occurs as a result of adaptation of genetically unstable cancer cells, in an ectopic conducive environment. Oral metastasis in spite of being unusual or rare represents around 25% of the first signs of metastatic spread. Literature says there are more number of cases of jaw bone metastasis reported than in the oral soft tissues. The most common primary organs metastasizing to the jaw bones and the oral soft tissues are the breast and the lungs respectively. The issue in diagnosing a metastatic tumor arises either when the patient does not reveal the history of the primary illness he or she may be suffering from or when he or she is unaware of it. Diagnosis in such situations is a challenge to the clinician or pathologist. Diagnosing any lymph node or distant metastasis from oral cancer is very important for the prognosis of the patient. In this review we have made an attempt, to explain some recent concepts of pathophysiology of the metastatic process, the clinical manifestations of metastatic tumors to the oral region and to discuss their diagnostic workup. PMID:25095855

  19. Cell stiffness is a biomarker of the metastatic potential of ovarian cancer cells

    NASA Astrophysics Data System (ADS)

    Xu, Wenwei; Mezencev, Roman; Kim, Byungkyu; Wang, Lijuan; McDonald, John; Sulchek, Todd; Sulchek Team; McDonald Team

    2013-03-01

    The metastatic potential of cells is an important parameter in the design of optimal strategies for the personalized treatment of cancer. Using atomic force microscopy (AFM), we show that ovarian cancer cells are generally softer and display lower intrinsic variability in cell stiffness than non-malignant ovarian epithelial cells. A detailed study of highly invasive ovarian cancer cells (HEY A8) and their less invasive parental cells (HEY), demonstrates that deformability can serve as an accurate biomarker of metastatic potential. Comparative gene expression profiling indicate that the reduced stiffness of highly metastatic HEY A8 cells is associated with actin cytoskeleton remodeling, microscopic examination of actin fiber structure in these cell lines is consistent with this prediction. Our results indicate that cell stiffness not only distinguishes ovarian cancer cells from non-malignant cells, but may also be a useful biomarker to evaluate the relative metastatic potential of ovarian and perhaps other types of cancer cells.

  20. Tumor infiltrating lymphocytes in ovarian cancer

    PubMed Central

    Santoiemma, Phillip P; Powell, Daniel J

    2015-01-01

    The accumulation of tumor infiltrating lymphocytes (TILs) in ovarian cancer is prognostic for increased survival while increases in immunosuppressive regulatory T-cells (Tregs) are associated with poor outcomes. Approaches that bolster tumor-reactive TILs may limit tumor progression. However, identifying tumor-reactive TILs in ovarian cancer has been challenging, though adoptive TIL therapy in patients has been encouraging. Other forms of TIL immunomodulation remain under investigation including Treg depletion, antibody-based checkpoint modification, activation and amplification using dendritic cells, antigen presenting cells or IL-2 cytokine culture, adjuvant cytokine injections, and gene-engineered T-cells. Many approaches to TIL manipulation inhibit ovarian cancer progression in preclinical or clinical studies as monotherapy. Here, we review the impact of TILs in ovarian cancer and attempts to mobilize TILs to halt tumor progression. We conclude that effective TIL therapy for ovarian cancer is at the brink of translation and optimal TIL activity may require combined methodologies to deliver clinically-relevant treatment. PMID:25894333

  1. iTRAQ Quantitative Proteomic Comparison of Metastatic and Non-Metastatic Uveal Melanoma Tumors

    PubMed Central

    Crabb, John W.; Hu, Bo; Crabb, John S.; Triozzi, Pierre; Saunthararajah, Yogen; Singh, Arun D.

    2015-01-01

    Background Uveal melanoma is the most common malignancy of the adult eye. The overall mortality rate is high because this aggressive cancer often metastasizes before ophthalmic diagnosis. Quantitative proteomic analysis of primary metastasizing and non-metastasizing tumors was pursued for insights into mechanisms and biomarkers of uveal melanoma metastasis. Methods Eight metastatic and 7 non-metastatic human primary uveal melanoma tumors were analyzed by LC MS/MS iTRAQ technology with Bruch’s membrane/choroid complex from normal postmortem eyes as control tissue. Tryptic peptides from tumor and control proteins were labeled with iTRAQ tags, fractionated by cation exchange chromatography, and analyzed by LC MS/MS. Protein identification utilized the Mascot search engine and the human Uni-Prot/Swiss-Protein database with false discovery ≤ 1%; protein quantitation utilized the Mascot weighted average method. Proteins designated differentially expressed exhibited quantitative differences (p ≤ 0.05, t-test) in a training set of five metastatic and five non-metastatic tumors. Logistic regression models developed from the training set were used to classify the metastatic status of five independent tumors. Results Of 1644 proteins identified and quantified in 5 metastatic and 5 non-metastatic tumors, 12 proteins were found uniquely in ≥ 3 metastatic tumors, 28 were found significantly elevated and 30 significantly decreased only in metastatic tumors, and 31 were designated differentially expressed between metastatic and non-metastatic tumors. Logistic regression modeling of differentially expressed collagen alpha-3(VI) and heat shock protein beta-1 allowed correct prediction of metastasis status for each of five independent tumor specimens. Conclusions The present data provide new clues to molecular differences in metastatic and non-metastatic uveal melanoma tumors. While sample size is limited and validation required, the results support collagen alpha-3(VI) and

  2. Sister Mary Joseph Nodule as a First Manifestation of a Metastatic Ovarian Cancer

    PubMed Central

    Ogino, Mai; Kinuta, Takatoshi; Hori, Masateru; Mori, Tatsuo

    2016-01-01

    A 76-year-old female presented to our hospital with a 2 cm firm, nontender, protuberant umbilical nodule. She received treatment with antibiotics for suspected granuloma, with no improvement after two months. High levels of CA125 as well as an ovarian cyst and intrathoracic and intra-abdominal lesions on imaging studies made us suspect an ovarian cancer with a Sister Mary Joseph nodule (SMJN) and other metastases. A bilateral salpingo-oophorectomy and umbilical and omentum tumor resections were performed and a metastatic ovarian serous adenocarcinoma was diagnosed by histopathology. After surgery, the patient received chemotherapy with paclitaxel, carboplatin, and bevacizumab; however paclitaxel allergy was observed. As a result, chemotherapy continued with carboplatin and bevacizumab every three weeks for a total of 6 courses. Currently, she is still undergoing treatment with bevacizumab and CA125 levels have been progressively decreasing. SMJN is a rare umbilical metastasis which needs to be considered as a differential diagnosis in the presence of an umbilical tumor for prompt treatment initiation.

  3. Mucinous ovarian tumors associated with mucinous adenocarcinomas of the cervix. A clinicopathological analysis of 16 cases.

    PubMed

    Young, R H; Scully, R E

    1988-01-01

    Sixteen cases of mucinous adenocarcinoma of the cervix that were associated with a mucinous tumor of one or both ovaries are reported. The patients ranged from 25 to 70 (average, 44) years of age; two of them had the Peutz-Jeghers syndrome. Eight patients complained of abdominal swelling; most of the remainder had symptoms of uterine origin. Twelve patients had bilateral and four had unilateral ovarian tumors, which were typically large and cystic. Microscopic examination of most of the ovarian tumors revealed various combinations of benign-appearing, borderline, and carcinomatous mucinous epithelium within the same specimen. Most of the cervical tumors were deeply invasive; 10 of them were of the adenoma malignum type. Although there were varying degrees of uncertainty in individual cases, consideration of several features including the extent and distribution of disease in the abdomen, the comparative histology of the tumors, and the pattern of ovarian involvement suggested that 10 of the ovarian tumors were independent primary tumors, three were metastatic from the cervix, and in three cases the ovaries contained both primary and metastatic tumors. PMID:2840404

  4. Regulatory T cells actively infiltrate metastatic brain tumors.

    PubMed

    Sugihara, Adam Quasar; Rolle, Cleo E; Lesniak, Maciej S

    2009-06-01

    Regulatory T cells (CD4+CD25+FoxP3+, Treg) have been shown to play a major role in suppression of the immune response to malignant gliomas. In this study, we investigated the kinetics of Treg infiltration in metastatic brain tumor models, including melanoma, breast and colon cancers. Our data indicate that both CD4+ and Treg infiltration are significantly increased throughout the time of metastatic tumor progression. These findings were recapitulated in human CNS tumor samples of metastatic melanoma and non-small cell lung carcinoma. Collectively, these data support investigating immunotherapeutic strategies targeting Treg in metastatic CNS tumors. PMID:19424570

  5. [Diagnosis of presumed benign ovarian tumors].

    PubMed

    Laculle-Massin, C; Collinet, P; Faye, N

    2013-12-01

    Symptoms of presumed benign ovarian tumors (PBOT) are not specific (LE4). Personal or family history of gynecological cancers can guide the diagnostic strategy. Clinical examination is ineffective for positive, topographic and etiologic diagnosis of PBOT (LE4). Signs of hormonal impregnation may refer to certain types of tumors (LE4). For any patient presenting with a pelvic mass, pelvic ultrasound is in the first-line exam (grade A); it can classify most ovarian tumors. In case of pure liquid unilocular mass smaller than 7 cm, ultrasound is sufficient to characterize the mass (grade A). In case of indeterminate or complex ovarian mass on ultrasound, MRI is useful to characterize the mass (LE2). Beyond 7 cm, the diagnostic performance of ultrasound decreases (LE2). When a non-unilocular liquid ovarian formation is characterized using ultrasound as determinate mass, ultrasound scan is the only exam recommended (grade B). MRI is indicated as a second-line scan for indeterminate masses or greater than 7 cm (grade B). Cyst puncture for diagnostic purposes has no place in the diagnostic strategy of ovarian cysts (grade C). In case of PBOT in pre-pubertal period, dosing biomarkers is useful but should not delay care. In adult women with PBOT, the measurement of CA125 is not recommended for first-line diagnosis (grade C). Current literature data are not sufficient to specify the diagnostic strategy for an ovarian tumor discovered incidentally during laparoscopy. In case of discovery of a high CA125 value, pelvic ultrasound is the first-line examination. The literature data are still limited to define a CA125 threshold value requiring further exploration or special monitoring, in case of normal pelvic ultrasound. PMID:24210239

  6. Dual HER/VEGF receptor targeting inhibits in vivo ovarian cancer tumor growth.

    PubMed

    Becker, Marc A; Farzan, Thahir; Harrington, Sean C; Krempski, James W; Weroha, S John; Hou, Xiaonan; Kalli, Kimberly R; Wong, Tai W; Haluska, Paul

    2013-12-01

    Ovarian cancer mortality ranks highest among all gynecologic cancers with growth factor pathways playing an integral role in tumorigenesis, metastatic dissemination, and therapeutic resistance. The HER and VEGF receptor (VEGFR) are both overexpressed and/or aberrantly activated in subsets of ovarian tumors. While agents targeting either the HER or VEGF pathways alone have been investigated, the impact of these agents have not led to overall survival benefit in ovarian cancer. We tested the hypothesis that cotargeting HER and VEGFR would maximize antitumor efficacy at tolerable doses. To this end, ovarian cancer xenografts grown intraperitoneally in athymic nude mice were tested in response to AC480 (pan-HER inhibitor, "HERi"), cediranib (pan-VEGFR inhibitor "VEGFRi"), or BMS-690514 (combined HER/VEGFR inhibitor "EVRi"). EVRi was superior to both HERi and VEGFRi in terms of tumor growth, final tumor weight, and progression-free survival. Correlative tumor studies employing phosphoproteomic antibody arrays revealed distinct agent-specific alterations, with EVRi inducing the greatest overall effect on growth factor signaling. These data suggest that simultaneous inhibition of HER and VEGFR may benefit select subsets of ovarian cancer tumors. To this end, we derived a novel HER/VEGF signature that correlated with poor overall survival in high-grade, late stage, serous ovarian cancer patient tumors. PMID:24130056

  7. Cystic Meningioma Masquerading as a Metastatic Tumor: A Case Report.

    PubMed

    Ramanathan, Nithya; Kamaruddin, Khairul Azmi; Othman, Aizzat; Mustafa, Fadhli; Awang, Mohamed Saufi

    2016-05-01

    Cystic meningioma is a rare form of intracranial meningioma. Meningiomas are typically solid tumors but may rarely have cystic components. The diagnosis of cystic meningioma is clinically challenging as the finding of multiple intra-axial tumors, including metastatic tumors, is relatively common. We report a case of cystic meningioma initially diagnosed as a metastatic tumor from a recurrence of acute lymphoid leukemia. However, postoperative histopathological examination demonstrated an atypical meningioma. PMID:27418876

  8. Cystic Meningioma Masquerading as a Metastatic Tumor: A Case Report

    PubMed Central

    Ramanathan, Nithya; Kamaruddin, Khairul Azmi; Othman, Aizzat; Mustafa, Fadhli; Awang, Mohamed Saufi

    2016-01-01

    Cystic meningioma is a rare form of intracranial meningioma. Meningiomas are typically solid tumors but may rarely have cystic components. The diagnosis of cystic meningioma is clinically challenging as the finding of multiple intra-axial tumors, including metastatic tumors, is relatively common. We report a case of cystic meningioma initially diagnosed as a metastatic tumor from a recurrence of acute lymphoid leukemia. However, postoperative histopathological examination demonstrated an atypical meningioma.

  9. Identification of Metabolites in the Normal Ovary and Their Transformation in Primary and Metastatic Ovarian Cancer

    PubMed Central

    Fong, Miranda Y.; McDunn, Jonathan; Kakar, Sham S.

    2011-01-01

    In this study, we characterized the metabolome of the human ovary and identified metabolic alternations that coincide with primary epithelial ovarian cancer (EOC) and metastatic tumors resulting from primary ovarian cancer (MOC) using three analytical platforms: gas chromatography mass spectrometry (GC/MS) and liquid chromatography tandem mass spectrometry (LC/MS/MS) using buffer systems and instrument settings to catalog positive or negative ions. The human ovarian metabolome was found to contain 364 biochemicals and upon transformation of the ovary caused changes in energy utilization, altering metabolites associated with glycolysis and β-oxidation of fatty acids—such as carnitine (1.79 fold in EOC, p<0.001; 1.88 fold in MOC, p<0.001), acetylcarnitine (1.75 fold in EOC, p<0.001; 2.39 fold in MOC, p<0.001), and butyrylcarnitine (3.62 fold, p<0.0094 in EOC; 7.88 fold, p<0.001 in MOC). There were also significant changes in phenylalanine catabolism marked by increases in phenylpyruvate (4.21 fold; p = 0.0098) and phenyllactate (195.45 fold; p<0.0023) in EOC. Ovarian cancer also displayed an enhanced oxidative stress response as indicated by increases in 2-aminobutyrate in EOC (1.46 fold, p = 0.0316) and in MOC (2.25 fold, p<0.001) and several isoforms of tocopherols. We have also identified novel metabolites in the ovary, specifically N-acetylasparate and N-acetyl-aspartyl-glutamate, whose role in ovarian physiology has yet to be determined. These data enhance our understanding of the diverse biochemistry of the human ovary and demonstrate metabolic alterations upon transformation. Furthermore, metabolites with significant changes between groups provide insight into biochemical consequences of transformation and are candidate biomarkers of ovarian oncogenesis. Validation studies are warranted to determine whether these compounds have clinical utility in the diagnosis or clinical management of ovarian cancer patients. PMID:21625518

  10. Romidepsin in Treating Patients With Locally Advanced or Metastatic Neuroendocrine Tumors

    ClinicalTrials.gov

    2013-06-03

    Gastrinoma; Glucagonoma; Insulinoma; Metastatic Gastrointestinal Carcinoid Tumor; Pancreatic Polypeptide Tumor; Pulmonary Carcinoid Tumor; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Islet Cell Carcinoma; Regional Gastrointestinal Carcinoid Tumor; Somatostatinoma

  11. [Palliative radiotherapy for metastatic bone tumor].

    PubMed

    Yoshida, Kenji; Hiratsuka, Junichi

    2006-04-01

    Bone metastases are one of the most common conditions requiring radiation therapy today. Its main aim is relief of bone pain, prevention of pathological bone fractures as well as its healing, with anticipated effect upon improving mobility, function, and quality of life. For localized bone pain, external beam radiation therapy (EBRT) will be successful in reducing pain in some 80% of patients. However, optimal fraction dose and total doses of EBRT required for pain relief have been unknown. According to the recent reports, carbon ion radiotherapy seems to be a safe and effective modality in the management of metastatic bone tumor not eligible for conventional EBRT. For scattered painful metastases, the systemic administration of radioisotopes is thought to be effective. PMID:16582516

  12. Clinicopathologic and immunohistochemical profile of ovarian metastases from colorectal carcinoma

    PubMed Central

    Kir, Gozde; Gurbuz, Ayse; Karateke, Ates; Kir, Mustafa

    2010-01-01

    Metastasis of colorectal adenocarcinoma of the ovary is not an uncommon occurrence and ovarian metastases from colorectal carcinoma frequently mimic endometrioid and mucinous primary ovarian carcinoma. The clinical and pathologic features of metastatic colorectal adenocarcinoma involving the ovary is reviewed with particular focus on the diagnostic challenge of distinguishing these secondary ovarian tumors from primary ovarian neoplasm. Immunohistochemical stains that may be useful in the differential diagnosis of metastatic colorectal tumors to the ovary and primary ovarian tumors are detailed. PMID:21160859

  13. Near-infrared fluorescent imaging of metastatic ovarian cancer using folate receptor-targeted high-density lipoprotein nanocarriers

    PubMed Central

    Corbin, Ian R; Ng, Kenneth K; Ding, Lili; Jurisicova, Andrea; Zheng, Gang

    2013-01-01

    Aim The targeting efficiency of folate receptor-α (FR-α)-targeted high-density lipoprotein nanoparticles (HDL NPs) was evaluated in a syngeneic mouse model of ovarian cancer. Materials & methods Folic acid was conjugated to the surface of fluorescent-labeled HDL NPs. In vivo tumor targeting of folic acid-HDL NPs and HDL NPs were evaluated in mice with metastatic ovarian cancer following intravenous or intraperitoneal (ip.) administration. Results & discussion Intravenous FR-α-targeted HDL resulted in high uptake of the fluorescent nanoparticle in host liver and spleen. The ip. injection of fluorescent HDL produced moderate fluorescence throughout the abdomen. Conversely, animals receiving the ip. FR-α-targeted HDL showed a high fluorescence signal in ovarian tumors, surpassing that seen in all of the host tissues. Conclusion The authors' findings demonstrate that the combination of local–regional ip. administration and FR-α-directed nanoparticles provides an enhanced approach to selectively targeting ovarian cancer cells for drug treatment. PMID:23067398

  14. Laser immunotherapy in treatment of metastatic prostate tumors in rats

    NASA Astrophysics Data System (ADS)

    Chen, Wei R.; Ritchey, Jerry W.; Bartles, Kenneth E.; Lucroy, Michael D.; Liu, Hong; Nordquist, Robert E.

    2002-07-01

    Laser immunotherapy is a special cancer treatment modality using an intratumor injection of a special formulation consisting of a novel immunoadjuvant and a laser-absorbing dye, followed by a non-invasive near-IR laser irradiation. Our early experiments using a metastatic mammary rat tumor model showed that laser immunotherapy could cause acute selective photothermal tumor destruction and induce a systemic, long-term specific anti-tumor immunity. In the current study, laser immunotherapy was used to treat metastatic prostate tumors in Copenhagen male rats. The transplantable tumors metastasize mainly to the lung and the lung cancer is usually the cause of death. Two experimental were performed in our study. The first was to study the effect of laser immunotherapy on the tumor burdens, both the primary and the metastasis in the lung. The second was to study the effect of laser immunotherapy on the long-term survival of the tumor-bearing rats. For comparison, some rat tumors were also treated by the laser-dye combination to study the photothermal effect. Tour results showed that both the photothermal effect and the laser immunotherapy could slow the growth of primary tumors and the metastatic tumors. The laser-dye-immunoadjuvant treatment resulted in more than 20 percent long-term survival rate in tumor-bearing rats. Our experimental results indicate that the laser immunotherapy has a great potential in treating metastatic tumors.

  15. Hepatic metastatic disease in pediatric and adolescent solid tumors

    PubMed Central

    Fernandez-Pineda, Israel; Sandoval, John A; Davidoff, Andrew M

    2015-01-01

    The management of hepatic metastatic disease from solid tumors in adults has been extensively described and resection of metastatic liver lesions from colorectal adenocarcinoma, renal adenocarcinoma, breast cancer, testicular cancer, and neuroendocrine tumors (NET) have demonstrated therapeutic benefits in select patients. However, there are few reports in the literature on the management of hepatic metastatic disease in the pediatric and adolescent populations and the effectiveness of hepatic metastasectomy. This may be due to the much lower incidence of pediatric malignancies and the higher chemosensitivity of childhood tumors which make hepatic metastasectomy less likely to be required. We review liver involvement with metastatic disease from the main pediatric solid tumors, including neuroblastoma and Wilms tumor focusing on the management and treatment options. We also review other solid malignant tumors which may have liver metastases including germ cell tumors, gastrointestinal stromal tumors, osteosarcoma, desmoplastic small round cell tumors and NET. However, these histological subtypes are so rare in the pediatric and adolescent populations that the exact incidence and best management of hepatic metastatic disease are unknown and can only be extrapolated from adult series. PMID:26207162

  16. General Information about Ovarian Low Malignant Potential Tumors

    MedlinePlus

    ... Malignant Potential Tumors Treatment (PDQ®)–Patient Version General Information About Ovarian Low Malignant Potential Tumors Go to ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  17. Detection of metastatic tumors after γ-irradiation using longitudinal molecular imaging and gene expression profiling of metastatic tumor nodules.

    PubMed

    Jang, Su Jin; Kang, Joo Hyun; Lee, Yong Jin; Kim, Kwang Il; Lee, Tae Sup; Choe, Jae Gol; Lim, Sang Moo

    2016-04-01

    A few recent reports have indicated that metastatic growth of several human cancer cells could be promoted by radiotherapy. C6-L cells expressing the firefly luciferase (fLuc) gene were implanted subcutaneously into the right thigh of BALB/c nu/nu mice. C6-L xenograft mice were treated locally with 50-Gy γ-irradiation (γ-IR) in five 10-Gy fractions. Metastatic tumors were evaluated after γ-IR by imaging techniques. Total RNA from non-irradiated primary tumor (NRPT), γ-irradiated primary tumor (RPT), and three metastatic lung nodule was isolated and analyzed by microarray. Metastatic lung nodules were detected by BLI and PET/CT after 6-9 weeks of γ-IR in 6 (17.1%) of the 35 mice. The images clearly demonstrated high [18F]FLT and [18F]FDG uptake into metastatic lung nodules. Whole mRNA expression patterns were analyzed by microarray to elucidate the changes among NRPT, RPT and metastatic lung nodules after γ-IR. In particular, expression changes in the cancer stem cell markers were highly significant in RPT. We observed the metastatic tumors after γ-IR in a tumor-bearing animal model using molecular imaging methods and analyzed the gene expression profile to elucidate genetic changes after γ-IR. PMID:26892334

  18. Detection of metastatic tumors after γ-irradiation using longitudinal molecular imaging and gene expression profiling of metastatic tumor nodules

    PubMed Central

    JANG, SU JIN; KANG, JOO HYUN; LEE, YONG JIN; KIM, KWANG IL; LEE, TAE SUP; CHOE, JAE GOL; LIM, SANG MOO

    2016-01-01

    A few recent reports have indicated that metastatic growth of several human cancer cells could be promoted by radiotherapy. C6-L cells expressing the firefly luciferase (fLuc) gene were implanted subcutaneously into the right thigh of BALB/c nu/nu mice. C6-L xenograft mice were treated locally with 50-Gy γ-irradiation (γ-IR) in five 10-Gy fractions. Metastatic tumors were evaluated after γ-IR by imaging techniques. Total RNA from non-irradiated primary tumor (NRPT), γ-irradiated primary tumor (RPT), and three metastatic lung nodule was isolated and analyzed by microarray. Metastatic lung nodules were detected by BLI and PET/CT after 6–9 weeks of γ-IR in 6 (17.1%) of the 35 mice. The images clearly demonstrated high [18F]FLT and [18F]FDG uptake into metastatic lung nodules. Whole mRNA expression patterns were analyzed by microarray to elucidate the changes among NRPT, RPT and metastatic lung nodules after γ-IR. In particular, expression changes in the cancer stem cell markers were highly significant in RPT. We observed the metastatic tumors after γ-IR in a tumor-bearing animal model using molecular imaging methods and analyzed the gene expression profile to elucidate genetic changes after γ-IR. PMID:26892334

  19. Treatment of ovarian endodermal sinus tumor to preserve fertility.

    PubMed

    Chang, Yi-Wen; Chao, Kuan-Chong; Sung, Pi-Lin; Li, Wai Hou; Wang, Peng-Hui

    2013-02-01

    Endodermal sinus tumor, also known as yolk sac tumor (YST), is a malignant germ cell tumor that most frequently occurs in the testis, the ovary, and sacrococcygeal areas in children. YSTs are highly aggressive and because of the early metastatic or invasive pattern, their prognosis has been poor. Treatment methods for YSTs are usually intensive, including multiagent chemotherapy, and have shown to improve patient survival significantly; therefore, it is important to consider the reproductive function of these patients with long-term survival. Herein, we present the case of a 31-year-old female, who was diagnosed with unilateral ovarian YST at the age of 13. The patient was treated with fertility-sparing surgery and postoperative adjuvant chemotherapy. During the subsequent long-term follow-up, she was not only free of disease, but also had a successful, naturally conceived pregnancy at 31 years of age. We, therefore, conclude that YST is a curable disease, and that fertility-preservation surgery and subsequent immediate combination chemotherapy is the treatment of choice. PMID:23351423

  20. Belinostat in Treating Patients With Advanced Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer or Ovarian Low Malignant Potential Tumors

    ClinicalTrials.gov

    2013-04-11

    Fallopian Tube Cancer; Primary Peritoneal Cavity Cancer; Recurrent Borderline Ovarian Surface Epithelial-stromal Tumor; Recurrent Ovarian Epithelial Cancer; Stage III Borderline Ovarian Surface Epithelial-stromal Tumor; Stage III Ovarian Epithelial Cancer; Stage IV Borderline Ovarian Surface Epithelial-stromal Tumor; Stage IV Ovarian Epithelial Cancer

  1. Microfocus of Anaplastic Carcinoma Arising in Mural Nodule of Ovarian Mucinous Borderline Tumor With Very Rapid and Fatal Outcome.

    PubMed

    Mhawech-Fauceglia, Paulette; Ramzan, Amin; Walia, Saloni; Pham, Huyen Q; Yessaian, Annie

    2016-07-01

    A 36-yr-old woman presented with abdominal discomfort. A computed tomography scan revealed a large left cystic and solid pelvic mass without evidence of metastatic disease. Total hysterectomy with bilateral salpingo-oophorectomy and tumor staging was performed. Grossly, the ovarian mass measured 20×18 cm and the cut surface was multiloculated with 1 single mural nodule measuring 2×1.5 cm. The histologic diagnosis of ovarian mucinous borderline tumor with a microfocus of anaplastic carcinoma arising in sarcoma-like mural nodule, FIGO Stage IA was rendered. After 3 mo, the patient returned with symptomatic anemia. A computed tomography scan showed enlarged retroperitoneal and pelvic lymph nodes. Image-guided biopsy of the pelvic lymph node showed a metastatic anaplastic carcinoma from her primary ovarian carcinoma. Chemotherapy was initiated, but the patient developed fulminant disseminated intravascular coagulation within <1 wk of her presentation which was fatal. PMID:26598983

  2. FOXL2 molecular status in adult granulosa cell tumors of the ovary: A study of primary and metastatic cases

    PubMed Central

    Zannoni, Gian Franco; Improta, Giuseppina; Petrillo, Marco; Pettinato, Angela; Scambia, Giovanni; Fraggetta, Filippo

    2016-01-01

    Granulosa cell tumors (GCTs) of the ovary are uncommon neoplasms, accounting for ~5% of all malignant ovarian tumors. GCTs are a relatively homogeneous group of tumors, categorized into two distinct subtypes, juvenile GCT and adult GCT (AGCT), likely arising from a limited set of molecular events usually involving the disruption of pathways that regulate granulosa cell proliferation. In the present study, the presence of forkheadbox L2 (FOXL2) c.402C>G mutation was investigated in a series of 42 samples of primary and metastatic AGCT of the ovary. The samples consisted of 37 primary and 5 metastatic ovarian AGCTs from 37 patients. FOXL2 mutational status was evaluated using a pyrosequencing approach on 2.5-µm sections of formalin-fixed paraffin-embedded tissue. FOXL2 c.402C>G mutation was found in 33/37 (89.2%) primary AGCTs and in 4/5 (80.0%) metastases, with the molecular status of the metastases recapitulating that of the primary tumors (4 mutated cases and 1 wild-type case). Overall, FOXL2 mutation is present in the majority of primary and metastatic AGCTs, and could be used as a valid tool in the diagnosis of the disease and in cases of metastatic lesions from an unknown primary origin. Moreover the concordance of FOXL2 molecular status in primary and associated metastases suggests its early appearance and genomic stability in AGCT tumorigenesis. PMID:27446412

  3. Tumor cells as cellular vehicles to deliver gene therapies to metastatic tumors.

    PubMed

    García-Castro, Javier; Martínez-Palacio, Jesús; Lillo, Rosa; García-Sánchez, Félix; Alemany, Ramón; Madero, Luis; Bueren, Juan A; Ramírez, Manuel

    2005-04-01

    A long-pursued goal in cancer treatment is to deliver a therapy specifically to metastases. As a result of the disseminated nature of the metastatic disease, carrying the therapeutic agent to the sites of tumor growth represents a major step for success. We hypothesized that tumor cells injected intravenously (i.v.) into an animal with metastases would respond to many of the factors driving the metastatic process, and would target metastases. Using a model of spontaneous metastases, we report here that i.v. injected tumor cells localized on metastatic lesions. Based on this fact, we used genetically transduced tumor cells for tumor targeting of anticancer agents such as a suicide gene or an oncolytic virus, with evident antitumoral effect and negligible systemic toxicity. Therefore, autologous tumor cells may be used as cellular vehicles for systemic delivery of anticancer therapies to metastatic tumors. PMID:15650763

  4. Targeting JAK1/STAT3 signaling suppresses tumor progression and metastasis in a peritoneal model of human ovarian cancer

    PubMed Central

    Wen, Wei; Liang, Wei; Wu, Jun; Kowolik, Claudia M.; Buettner, Ralf; Scuto, Anna; Hsieh, Meng-Yin; Hong, Hao; Brown, Christine E.; Forman, Stephen J.; Horne, David; Morgan, Robert; Wakabayashi, Mark; Dellinger, Thanh H.; Han, Ernest S.; Yim, John H.; Jove, Richard

    2015-01-01

    JAK/STAT3 is one of the major signaling pathways that is aberrantly activated in ovarian cancer and associated with tumor progression and poor prognosis in ovarian cancer patients. In this study, we evaluated the therapeutic potential of targeting JAK/STAT3 signaling in ovarian cancer using a peritoneal dissemination mouse model. We developed this mouse model by injecting a metastatic human ovarian cancer cell line, SKOV3-M-Luc, into the peritoneal cavity of immunodeficient mice. This model displayed a phenotype similar to late stage ovarian cancer, including extensive peritoneal metastasis and ascites production. The constitutive activation of STAT3 in human ovarian cancer cells appeared to be mediated by an autocrine-cytokine loop involving the IL-6 family of cytokines and JAK1 kinase. shRNA-mediated knockdown of JAK1 or STAT3 in ovarian cancer cells led to reduced tumor growth, decreased peritoneal dissemination and diminished ascites production, suggesting a critical role of STAT3 in ovarian cancer progression. Similar results were obtained when a small-molecule inhibitor (JAKi) of the JAK1 kinase was used to treat ovarian cancer in this model. In addition, we found that the expression level of IL-6 was correlated with activation of STAT3 in ovarian cancer cells both in vitro and in vivo, suggesting a potential application of IL-6 as a biomarker. Altogether, our results demonstrate that targeting JAK1/STAT3, using shRNA knockdown or a small molecule inhibitor, effectively suppressed ovarian tumor progression and, therefore, could be a potential novel therapeutic approach for treating advanced ovarian cancer. PMID:25319391

  5. Tumor microenvironment: The culprit for ovarian cancer metastasis?

    PubMed

    Luo, Zhongyue; Wang, Qiu; Lau, Wayne Bond; Lau, Bonnie; Xu, Lian; Zhao, Linjie; Yang, Huiliang; Feng, Min; Xuan, Yu; Yang, Yanfei; Lei, Lingzi; Wang, Chenlu; Yi, Tao; Zhao, Xia; Wei, Yuquan; Zhou, Shengtao

    2016-07-28

    Despite chemotherapy and surgical debulking options, ovarian cancer recurs and disseminates frequently, with poor prognosis. However, the molecular mechanisms underlying ovarian cancer metastasis still remain unelucidated. The tumor microenvironment, consisting of stromal cells (including fibroblasts, macrophages, regulatory T cells, myeloid-derived suppressor cells, endothelial cells, pericytes and platelets), the extracellular matrix component (EMC) (including inflammatory cytokines, chemokines, matrix metalloproteinases, integrins, and other secreted molecules) and exosomes (small extracellular vesicles loaded with molecules), establishes an autocrine-paracrine communication circuit that reinforces invasion and cancer cell metastasis via reciprocal signaling. Recent evidences have unraveled the significant contribution of tumor microenvironment to ovarian cancer metastasis. In this review, we provide a comprehensive landscape of the reciprocity between tumor stroma and ovarian cancer cells upon metastasis, aiming to offer novel clues on the development of novel diagnostic biomarkers and therapeutic targets for ovarian cancer in future clinical practice. PMID:27131957

  6. Carboplatin and Gemcitabine Hydrochloride With or Without ATR Kinase Inhibitor VX-970 in Treating Patients With Recurrent and Metastatic Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2016-06-21

    High Grade Ovarian Serous Adenocarcinoma; Ovarian Endometrioid Tumor; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

  7. Method for Recovery and Immunoaffinity Enrichment of Membrane Proteins Illustrated with Metastatic Ovarian Cancer Tissues

    PubMed Central

    Schneider, Luke V.; Likhte, Varsha; Wright, William H.; Chu, Frances; Cambron, Emma; Baldwin-Burnett, Anne; Krakow, Jessica; Smejkal, Gary B.

    2012-01-01

    Integral membrane proteins play key biological roles in cell signaling, transport, and pathogen invasion. However, quantitative clinical assays for this critical class of proteins remain elusive and are generally limited to serum-soluble extracellular fragments. Furthermore, classic proteomic approaches to membrane protein analysis typically involve proteolytic digestion of the soluble pieces, resulting in separation of intra- and extracellular segments and significant informational loss. In this paper, we describe the development of a new method for the quantitative extraction of intact integral membrane proteins (including GPCRs) from solid metastatic ovarian tumors using pressure cycling technology in combination with a new (ProteoSolve-TD) buffer system. This new extraction buffer is compatible with immunoaffinity methods (e.g., ELISA and immunoaffinity chromatography), as well as conventional proteomic techniques (e.g., 2D gels, western blots). We demonstrate near quantitative recovery of membrane proteins EDG2, EDG4, FASLG, KDR, and LAMP-3 by western blots. We have also adapted commercial ELISAs for serum-soluble membrane protein fragments (e.g., sVEGFR2) to measure the tissue titers of their transmembrane progenitors. Finally, we demonstrate the compatibility of the new buffers with immunoaffinity enrichment/mass spectrometric characterization of tissue proteins. PMID:22919487

  8. Dasatinib, Ifosfamide, Carboplatin, and Etoposide in Treating Young Patients With Metastatic or Recurrent Malignant Solid Tumors

    ClinicalTrials.gov

    2016-08-10

    Brain and Central Nervous System Tumors; Childhood Germ Cell Tumor; Extragonadal Germ Cell Tumor; Kidney Cancer; Liver Cancer; Lymphoma; Neuroblastoma; Ovarian Cancer; Sarcoma; Testicular Germ Cell Tumor; Unspecified Childhood Solid Tumor, Protocol Specific

  9. Cytochrome P450 CYP1B1 over-expression in primary and metastatic ovarian cancer

    PubMed Central

    McFadyen, M C E; Cruickshank, M E; Miller, I D; McLeod, H L; Melvin, W T; Haites, N E; Parkin, D; Murray, G I

    2001-01-01

    Ovarian cancer is the most frequent cause of death from gynaecological malignancies world wide. Little improvement has been made in the long-term outcome of this disease, with the 5-year survival of patients only 30%. This poor prognosis is due to the late presentation of the disease and to the unpredictable response of ovarian cancer to chemotherapy. The cytochrome P450 enzymes are a superfamily of haemoproteins, known to be involved in the metabolic activation and/or detoxification of a number of anti-cancer drugs. CYP1B1 is a tumour-related form of cytochrome P450 which is over expressed in a wide variety of primary tumours of different histological type. The presence of CYP1B1 may be of importance in the modulation of these tumours to anti-cancer drugs. We have conducted a comprehensive immunohistochemical investigation, into the presence of cytochrome P450 CYP1B1 in primary and metastatic ovarian cancer. The key findings of this study are the increased expression of CYP1B1 in the majority of ovarian cancers investigated (92%), with a strong correlation demonstrated between CYP1B1 expression in both primary and metastatic ovarian cancer (P= 0.005 Spearman's rank correlation test). In contrast no detectable CYP1B1 was found in normal ovary. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11461084

  10. Ovarian tumors in postmenopausal breast cancer patients treated with tamoxifen.

    PubMed

    Cohen, I; Beyth, Y; Tepper, R; Shapira, J; Zalel, Y; Figer, A; Cordoba, M; Yigael, D; Altaras, M M

    1996-01-01

    From September 1, 1989, to November 30, 1994, 175 menopausal breast cancer patients treated with tamoxifen were followed at the authors' institutions. During this period. 16 (9.1%) underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy, for various indications. Of these, 10 (62.5%) had either uni- or bilateral ovarian tumors. The analysis of surgical findings showed an incidence of 5.7% (10/175) ovarian tumors among all the patients. In 2 (20%), the ovarian masses displayed enlargement over a relatively short period while on treatment. In 5 (50%) patients, the findings were bilateral. All tumors were detectable by ultrasonography, except four serous cystadenomas found in 3 women. The mean duration of tamoxifen treatment was 36.6 +/- 24.9 (range 9-86) months. The rate of 5.7% for ovarian tumors, in this selected group of patients, is four to five times higher than that reported for similar pathologic conditions detected by general screening with ultrasonographic scans among nonselected, asymptomatic, and untreated postmenopausal women. Two possibilities should be considered in the development of ovarian tumors coinciding with tamoxifen treatment; (1) women with breast malignancy are prone to develop benign or malignant ovarian tumors in relation to genetic factors, regardless of tamoxifen treatment; and (2) tamoxifen may stimulate enlargement of such tumors and may even cause them. PMID:8557228

  11. The role of intratumoral lymphovascular density in distinguishing primary from secondary mucinous ovarian tumors

    PubMed Central

    de Lacerda Almeida, Bernardo Gomes; Bacchi, Carlos E; Carvalho, Jesus P; Ferreira, Cristiane R; Carvalho, Filomena M

    2014-01-01

    OBJECTIVE: Ovarian mucinous metastases commonly present as the first sign of the disease and are capable of simulating primary tumors. Our aim was to investigate the role of intratumoral lymphatic vascular density together with other surgical-pathological features in distinguishing primary from secondary mucinous ovarian tumors. METHODS: A total of 124 cases of mucinous tumors in the ovary (63 primary and 61 metastatic) were compared according to their clinicopathological features and immunohistochemical profiles. The intratumoral lymphatic vascular density was quantified by counting the number of vessels stained by the D2-40 antibody. RESULTS: Metastases occurred in older patients and were associated with a higher proportion of tumors smaller than 10.0 cm; bilaterality; extensive necrosis; extraovarian extension; increased expression of cytokeratin 20, CDX2, CA19.9 and MUC2; and decreased expression of cytokeratin 7, CA125 and MUC5AC. The lymphatic vascular density was increased among primary tumors. However, after multivariate analysis, the best predictors of a secondary tumor were a size of 10.0 cm or less, bilaterality and cytokeratin 7 negativity. Lack of MUC2 expression was an important factor excluding metastasis. CONCLUSIONS: The higher intratumoral lymphatic vascular density in primary tumors when compared with secondary lesions suggests differences in the microenvironment. However, considering the differential diagnosis, the best discriminator of a secondary tumor is the combination of tumor size, laterality and the pattern of expression of cytokeratin 7 and MUC2. PMID:25518016

  12. Ovarian Tumor Attachment, Invasion, and Vascularization Reflect Unique Microenvironments in the Peritoneum: Insights from Xenograft and Mathematical Models

    PubMed Central

    Steinkamp, Mara P.; Winner, Kimberly Kanigel; Davies, Suzy; Muller, Carolyn; Zhang, Yong; Hoffman, Robert M.; Shirinifard, Abbas; Moses, Melanie; Jiang, Yi; Wilson, Bridget S.

    2013-01-01

    Ovarian cancer relapse is often characterized by metastatic spread throughout the peritoneal cavity with tumors attached to multiple organs. In this study, interaction of ovarian cancer cells with the peritoneal tumor microenvironment was evaluated in a xenograft model based on intraperitoneal injection of fluorescent SKOV3.ip1 ovarian cancer cells. Intra-vital microscopy of mixed GFP-red fluorescent protein (RFP) cell populations injected into the peritoneum demonstrated that cancer cells aggregate and attach as mixed spheroids, emphasizing the importance of homotypic adhesion in tumor formation. Electron microscopy provided high resolution structural information about local attachment sites. Experimental measurements from the mouse model were used to build a three-dimensional cellular Potts ovarian tumor model (OvTM) that examines ovarian cancer cell attachment, chemotaxis, growth, and vascularization. OvTM simulations provide insight into the relative influence of cancer cell–cell adhesion, oxygen availability, and local architecture on tumor growth and morphology. Notably, tumors on the mesentery, omentum, or spleen readily invade the “open” architecture, while tumors attached to the gut encounter barriers that restrict invasion and instead rapidly expand into the peritoneal space. Simulations suggest that rapid neovascularization of SKOV3.ip1 tumors is triggered by constitutive release of angiogenic factors in the absence of hypoxia. This research highlights the importance of cellular adhesion and tumor microenvironment in the seeding of secondary ovarian tumors on diverse organs within the peritoneal cavity. Results of the OvTM simulations indicate that invasion is strongly influenced by features underlying the mesothelial lining at different sites, but is also affected by local production of chemotactic factors. The integrated in vivo mouse model and computer simulations provide a unique platform for evaluating targeted therapies for ovarian cancer

  13. Multiple embolic cerebral infarcts as the first manifestation of metastatic ovarian cancer.

    PubMed

    Bond, Laura M; Skrobo, Darko

    2015-01-01

    A 36-year-old woman presented to the emergency department with a 3-day history of an occipital headache associated with transient visual impairment and short-term memory loss. MRI of the brain showed innumerable focal embolic infarcts of differing ages, for which a cause could not be determined. The patient was discharged and readmitted 7 weeks later with acute aphasia and a right-sided hemiplegia. CT of the abdomen revealed a right-sided ovarian mass and prominent retroperitoneal nodes, which cytology confirmed to be metastatic ovarian cancer. PMID:26443095

  14. The value of SATB2 in the differential diagnosis of intestinal-type mucinous tumors of the ovary: primary vs metastatic.

    PubMed

    Perez Montiel, Delia; Arispe Angulo, Karen; Cantú-de León, David; Bornstein Quevedo, Leticia; Chanona Vilchis, José; Herrera Montalvo, Luis

    2015-08-01

    Primary mucinous adenocarcinomas of the ovary are a diagnostic challenge because their histologic and immunohistochemical features usually overlap with metastatic tumors. SATB2 is a recently identified protein with restricted expression in the glandular cells lining the lower gastrointestinal tract. The aim of this study is to examine the differential expression of SATB2 in primary and metastatic tumors of the ovary. Mucinous ovarian tumors of intestinal type were retrieved from the pathology files of the Instituto Nacional de Cancerología de México. A double reading of the hematoxylin and eosin-stained slides was performed to confirm the diagnosis, and a detailed review of the clinical chart was performed to define the primary origin of the tumor (ovarian vs metastatic). Immunohistochemical staining for CK20, CDX2, and SATB2 was performed and evaluated by 2 gynecopathologists. A total of 106 mucinous tumors were identified, 26 of which were considered to be metastatic, and 80 of which were primary ovarian tumors. All of the primary tumors that were not associated with cystic teratomas were negative for SATB2, and the 4 that were associated with a teratoma were positive for SATB2. All 20 of the metastatic tumors of the colon and appendix were positive for CK20, and 4 were positive for CK7. In addition, all 20 of these tumors were positive for SATB2, and 19 were positive for CDX2. SATB2 appears to be a useful marker for the diagnosis of primary vs metastatic mucinous intestinal-type neoplasms and is highly sensitive in detecting lower gastrointestinal tract metastasis. PMID:26059401

  15. Paclitaxel and Carboplatin or Bleomycin Sulfate, Etoposide Phosphate, and Cisplatin in Treating Patients With Advanced or Recurrent Sex Cord-Ovarian Stromal Tumors

    ClinicalTrials.gov

    2016-03-16

    Ovarian Granulosa Cell Tumor; Ovarian Gynandroblastoma; Ovarian Sertoli-Leydig Cell Tumor; Ovarian Sex Cord Tumor With Annular Tubules; Ovarian Sex Cord-Stromal Tumor; Ovarian Sex Cord-Stromal Tumor of Mixed or Unclassified Cell Types; Ovarian Steroid Cell Tumor

  16. Capnocytophaga Lung Abscess in a Patient with Metastatic Neuroendocrine Tumor

    PubMed Central

    Thirumala, Raghu; Babady, N. Esther; Kamboj, Mini; Chawla, Mohit

    2012-01-01

    Capnocytophaga species are known commensals of the oral cavity of humans and animals (mainly dogs and cats) and are a rare cause of respiratory tract infections. We report a case of cavitary lung abscess caused by a Capnocytophaga species in a patient with a metastatic neuroendocrine tumor. PMID:22075586

  17. Ovarian signet-ring stromal tumor: a potential diagnostic pitfall.

    PubMed

    Shaco-Levy, Ruthy; Kachko, Leonid; Mazor, Moshe; Piura, Benjamin

    2008-04-01

    Signet-ring stromal tumor is a rare ovarian neoplasm with only 10 reported cases in the literature. We report an unusual case of ovarian signet-ring stromal tumor in a 69-year-old woman who presented with right adnexal mass and underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. The diagnosis was based on histological, histochemical, immunohistochemical, and electron microscopy characteristics. The main significance is to differentiate this benign tumor from the highly malignant Krukenberg tumor, and this differential diagnosis is discussed. PMID:18417676

  18. A metastatic ovarian angiosarcoma mimicking hematologic neoplasia at diagnosis.

    PubMed

    Gaiolla, Rafael Dezen; Duarte, Ivison Xavier; Bacchi, Carlos Eduardo; Paiva, Carlos Eduardo

    2014-01-01

    Angiosarcomas are rare aggressive neoplasms of vascular endothelial origin with a high metastatic rate and poor prognosis. Involvement of the bone marrow by the angiosarcoma is exceedingly uncommon, and there have only been a few cases reported in the literature to date. Clinical manifestations and common laboratory findings of bone marrow involvement can mimic other more common bone marrow-replacing neoplasias such as lymphomas and acute leukemia. A definitive diagnosis is difficult to make from cytologic material, probably due to an associated bone marrow fibrosis, and requires bone marrow trephine biopsy with an immunohistochemical profile. Here we had the opportunity to study a case of metastatic angiosarcoma with positive cytologic findings and an unusual presentation that challenged its primary diagnosis. PMID:24847252

  19. A Metastatic Ovarian Angiosarcoma Mimicking Hematologic Neoplasia at Diagnosis

    PubMed Central

    Gaiolla, Rafael Dezen; Duarte, Ívison Xavier; Bacchi, Carlos Eduardo; Paiva, Carlos Eduardo

    2014-01-01

    Angiosarcomas are rare aggressive neoplasms of vascular endothelial origin with a high metastatic rate and poor prognosis. Involvement of the bone marrow by the angiosarcoma is exceedingly uncommon, and there have only been a few cases reported in the literature to date. Clinical manifestations and common laboratory findings of bone marrow involvement can mimic other more common bone marrow-replacing neoplasias such as lymphomas and acute leukemia. A definitive diagnosis is difficult to make from cytologic material, probably due to an associated bone marrow fibrosis, and requires bone marrow trephine biopsy with an immunohistochemical profile. Here we had the opportunity to study a case of metastatic angiosarcoma with positive cytologic findings and an unusual presentation that challenged its primary diagnosis. PMID:24847252

  20. Extracellular Vesicles from Metastatic Rat Prostate Tumors Prime the Normal Prostate Tissue to Facilitate Tumor Growth.

    PubMed

    Halin Bergström, Sofia; Hägglöf, Christina; Thysell, Elin; Bergh, Anders; Wikström, Pernilla; Lundholm, Marie

    2016-01-01

    Accumulating data indicates that tumor-derived extracellular vesicles (EVs) are responsible for tumor-promoting effects. However, if tumor EVs also prepare the tumor-bearing organ for subsequent tumor growth, and if this effect is different in low and high malignant tumors is not thoroughly explored. Here we used orthotopic rat Dunning R-3327 prostate tumors to compare the role of EVs from fast growing and metastatic MatLyLu (MLL) tumors with EVs from more indolent and non-metastatic Dunning G (G) tumors. Prostate tissue pre-conditioned with MLL-EVs in vivo facilitated G tumor establishment compared to G-EVs. MLL-EVs increased prostate epithelial proliferation and macrophage infiltration into the prostate compared to G-EVs. Both types of EVs increased macrophage endocytosis and the mRNA expression of genes associated with M2 polarization in vitro, with MLL-EVs giving the most pronounced effects. MLL-EVs also altered the mRNA expression of growth factors and cytokines in primary rat prostate fibroblasts compared to G-EVs, suggesting fibroblast activation. Our findings propose that EVs from metastatic tumors have the ability to prime the prostate tissue and enhance tumor growth to a higher extent than EVs from non-metastatic tumors. Identifying these differences could lead to novel therapeutic targets and potential prognostic markers for prostate cancer. PMID:27550147

  1. Extracellular Vesicles from Metastatic Rat Prostate Tumors Prime the Normal Prostate Tissue to Facilitate Tumor Growth

    PubMed Central

    Halin Bergström, Sofia; Hägglöf, Christina; Thysell, Elin; Bergh, Anders; Wikström, Pernilla; Lundholm, Marie

    2016-01-01

    Accumulating data indicates that tumor-derived extracellular vesicles (EVs) are responsible for tumor-promoting effects. However, if tumor EVs also prepare the tumor-bearing organ for subsequent tumor growth, and if this effect is different in low and high malignant tumors is not thoroughly explored. Here we used orthotopic rat Dunning R-3327 prostate tumors to compare the role of EVs from fast growing and metastatic MatLyLu (MLL) tumors with EVs from more indolent and non-metastatic Dunning G (G) tumors. Prostate tissue pre-conditioned with MLL-EVs in vivo facilitated G tumor establishment compared to G-EVs. MLL-EVs increased prostate epithelial proliferation and macrophage infiltration into the prostate compared to G-EVs. Both types of EVs increased macrophage endocytosis and the mRNA expression of genes associated with M2 polarization in vitro, with MLL-EVs giving the most pronounced effects. MLL-EVs also altered the mRNA expression of growth factors and cytokines in primary rat prostate fibroblasts compared to G-EVs, suggesting fibroblast activation. Our findings propose that EVs from metastatic tumors have the ability to prime the prostate tissue and enhance tumor growth to a higher extent than EVs from non-metastatic tumors. Identifying these differences could lead to novel therapeutic targets and potential prognostic markers for prostate cancer. PMID:27550147

  2. Bilateral ovarian mixed epithelial adenocarcinoma in a postmenopausal woman with unilateral ovarian yolk sac tumor component.

    PubMed

    Chen, Qin; Chen, Xiaoduan

    2014-01-01

    Ovarian yolk sac tumors (YSTs) usually occur in the young women and have been rarely documented in perimenopausal and postmenopausal women. The different age distribution supposes their complex nomenclature and histogenesis. We report a case of bilateral ovarian epithelial carcinoma with right ovarian YST component in a postmenopausal woman. The patient was treated by surgery and adjuvant combination chemotherapy of taxol and carboplatin for 6 courses and has been clinically free of tumor for 6 months. The correlation between the YST and the epithelial components always confuse us. Ovarian yolk sac tumors are not a discrete entity and represent a multifaceted group of neoplasms. The conjunction of multi antibodies help in differential diagnoses. In addition to a thorough case description, the literature concerning this entity is reviewed and discussed. PMID:25550883

  3. Serum-derived exosomes from mice with highly metastatic breast cancer transfer increased metastatic capacity to a poorly metastatic tumor.

    PubMed

    Gorczynski, Reginald M; Erin, Nuray; Zhu, Fang

    2016-02-01

    Altered interaction between CD200 and CD200R represents an example of "checkpoint blockade" disrupting an effective, tumor-directed, host response in murine breast cancer cells. In CD200R1KO mice, long-term cure of EMT6 breast cancer, including metastatic spread to lung and liver, was achieved in BALB/c mice. The reverse was observed with 4THM tumors, an aggressive, inflammatory breast cancer, with increased tumor metastasis in CD200R1KO. We explored possible explanations for this difference. We measured the frequency of circulating tumor cells (CTCs) in peripheral blood of tumor bearers, as well as lung/liver and draining lymph nodes. In some cases mice received infusions of exosomes from nontumor controls, or tumor bearers, with/without additional infusions of anticytokine antibodies. The measured frequency of circulating tumor cells (CTCs) in peripheral blood was equivalent in the two models in WT and CD200R1KO mice. Increased metastasis in EMT6 tumor bearers was seen in vivo following adoptive transfer of serum, or serum-derived exosomes, from 4THM tumor bearers, an effect which was attenuated by anti-IL-6, and anti-IL-17, but not anti-TNFα, antibody. Anti-IL-6 also attenuated enhanced migration of EMT6 cells in vitro induced by 4THM serum or exosomes, or recombinant IL-6. Exosome cytokine proteomic profiles responses in 4THM and EMT6 tumor-bearing mice were regulated by CD200:CD200R interactions, with attenuation of both IL-6 and IL-17 in 4THM CD200(tg) mice, and enhanced levels in 4THM CD200R1KO mice. We suggest these cytokines act on the microenvironment at sites within the host, and/or directly on tumor cells themselves, to increase metastatic potential. PMID:26725371

  4. Serum folate receptor alpha as a biomarker for ovarian cancer: Implications for diagnosis, prognosis and predicting its local tumor expression.

    PubMed

    Kurosaki, Akira; Hasegawa, Kosei; Kato, Tomomi; Abe, Kenji; Hanaoka, Tatsuya; Miyara, Akiko; O'Shannessy, Daniel J; Somers, Elizabeth B; Yasuda, Masanori; Sekino, Tetsuo; Fujiwara, Keiichi

    2016-04-15

    Folate receptor alpha (FRA) is a GPI-anchored glycoprotein and encoded by the FOLR1 gene. High expression of FRA is observed in specific malignant tumors of epithelial origin, including ovarian cancer, but exhibits very limited normal tissue expression, making it as an attractive target for the ovarian cancer therapy. FRA is known to shed from the cell surface into the circulation which allows for its measurement in the serum of patients. Recently, methods to detect the soluble form of FRA have been developed and serum FRA (sFRA) is considered a highly promising biomarker for ovarian cancer. We prospectively investigated the levels of sFRA in patients clinically suspected of having malignant ovarian tumors. A total of 231 patients were enrolled in this study and analyzed for sFRA as well as tumor expression of FRA by immunohistochemistry. High sFRA was predominantly observed in epithelial ovarian cancer patients, but not in patients with benign or borderline gynecological disease or metastatic ovarian tumors from advanced colorectal cancers. Levels of sFRA were highly correlated to clinical stage, tumor grade and histological type and demonstrated superior accuracy for the detection of ovarian cancer than did serum CA125. High sFRA was significantly associated with shorter progression-free survival in both early and advanced ovarian cancer patients. Finally, tumor FRA expression status was strongly correlated with sFRA levels. Taken together, these data suggest that sFRA might be a useful noninvasive serum biomarkers for future clinical trials assessing FRA-targeted therapy. PMID:26595060

  5. Preparation of a novel adenovirus formulation with artificial envelope of multilayer polymer-coatings: therapeutic effect on metastatic ovarian cancer.

    PubMed

    Yoshihara, Chieko; Hamada, Katsuyuki; Koyama, Yoshiyuki

    2010-03-01

    Layer-by-layer deposition of the ionic polymers onto adenovirus particles afforded the multilayer-coated virus vectors. The infectivity of the virus in the presence of anti-adenovirus antibody increased as the layer number and the viruses with five or six polymer layers allowed relatively high efficiency of reporter gene expression in vitro. Therapeutic effect of the intraperitoneal injection of the oncolytic adenovirus with quintal polymer multilayers on the mice bearing intraperitoneal metastatic ovarian cancer was examined. All the control mice injected with PBS died within 21 days after the tumor inoculation. On the other hand, the mice injected with the multilayer-coated oncolytic virus lived much longer and seven eighths of them lived >60 days without apparent accumulation of ascites. These approaches would open a new way to create a novel, safe and efficient viral gene therapy. PMID:20127013

  6. Metastatic tumors to the jaws and oral cavity.

    PubMed

    Kumar, Gs; Manjunatha, Bs

    2013-01-01

    Cancer is a disease involving complex multiple sequential irreversible dysregulated processes showing metastasis that results in morbidity and mortality. Metastasis is a complex biological course that begins with detachment of tumor cells from the primary tumor, spreading into the distant tissues and/or organs, invading through the lymphovascular structures followed by their survival in the circulation. Metastatic tumors to the oro-facial region are uncommon and may occur in the oral soft tissues or jawbones. The clinical presentation of metastatic tumors can be variable, which may lead to erroneous diagnosis or may create diagnostic dilemma. Therefore, they should be considered in the differential diagnosis of inflammatory and reactive lesions that are common to the oral region. Most of the literature on oral metastases involves either single case reports or reviews of these reported cases from scattered geographical areas. Hence this present article is an attempt to provide a detailed review of pathogenesis, epidemiological details including clinical and radiographic presentations, microscopic features and treatment of metastatic tumors to the jaws and oral cavity. PMID:23798834

  7. Metastatic Periampullary Tumor from Hepatocellular Carcinoma Presenting as Gastrointestinal Bleeding

    PubMed Central

    Nissen, Nicholas N.; Guindi, Maha; Jamil, Laith H.

    2015-01-01

    Periampullary tumors constitute a number of diverse neoplastic lesions located within 2 cm of the major duodenal papilla; among these, metastatic lesions account for only a small proportion of the periampullary tumors. To our knowledge, a metastatic periampullary tumor from hepatocellular carcinoma has never been reported. A 62-year-old male reported to our institute for fatigue and low hemoglobin. His medical history was remarkable for multifocal hepatocellular carcinoma (HCC) treated with selective transcatheter arterial chemoembolization (TACE). An esophagogastroduodenoscopy (EGD) was performed which revealed a periampullary mass. Histopathology was consistent with metastatic moderately differentiated HCC. Two endoloops were deployed around the base of the mass one month apart. The mass eventually sloughed off and patient's hemoglobin level stabilized. We postulated that periampullary metastasis in this patient was the result of tumor fragments migration through the biliary tracts and that TACE which increases tumor fragments burden might have played a contributory role. Metastasis of HCC to the gastrointestinal (GI) tract should be considered as a cause of GI bleeding. PMID:26064707

  8. Metastatic brain tumor from urothelial carcinoma of the prostatic urethra

    PubMed Central

    Morita, Kohei; Oda, Masashi; Koyanagi, Masaomi; Saiki, Masaaki

    2016-01-01

    Background: Urothelial carcinoma occurs in the bladder, upper urinary tract, and lower urinary tract, including prostatic urethra. A majority of the reported cases of intracranial metastasis from urothelial carcinoma originates from the bladder and upper urinary tract. Brain metastasis from urothelial carcinoma of the prostatic urethra has not yet been reported in the literature. Case Description: A 72-year-old male presented with a metastatic brain tumor and a 3-year history of urothelial carcinoma of the prostatic urethra treated with cystourethrectomy and chemotherapy with gemcitabine-cisplatin. Pathological diagnosis for tumor removal was compatible with metastatic brain tumor from urothelial carcinoma. Conclusion: Brain metastasis from urothelial carcinoma of the prostatic urethra has not yet been reported in the literature. It is an extremely rare case, however, we should be careful of brain metastasis during follow-up for urothelial carcinoma in the lower urinary tract. PMID:27512612

  9. Identification of Epithelial Ovarian Tumor-Specific Aptamers

    PubMed Central

    Benedetto, Gregory; Hamp, Timothy J.; Wesselman, Peter J.

    2015-01-01

    Ovarian cancer is often diagnosed in late stages with few treatment options and poor long-term prognosis. New clinical tools for early detection of ovarian malignancies will significantly help reduce mortality and improve current long-term survival rates. The objective of this work was to identify ovarian tumor-specific single-stranded DNA aptamers that bind to malignant ovarian tumor cells and internalize with high affinity and specificity. Aptamers can identify unique tumor biomarkers, can aid in early detection and diagnosis of neoplastic disorders, and can be functionalized by conjugation to small molecules. To identify aptamers from random single-stranded DNA pools (60 bases long), we used whole Cell-SELEX (systematic evolution of ligands by exponential enrichment) to enrich and isolate tumor-specific aptamers that bind to tumor-specific receptors in their native state on the cell surface. Next-Generation sequencing identified seven novel aptamers and detailed analyses of three are described. Aptamers bound to, and were internalized by, target Caov-3 cell populations, but not nontarget nonmalignant ovarian epithelial HOSE 6-3 cells or multiple other epithelial tumor cell lines. Furthermore, aptamers showed unique binding affinities with apparent dissociation constants (Kd) measuring in the submicromolar range supporting their physiological relevance and potential use in clinical applications. PMID:25894736

  10. Diagnosis, Treatment, and Follow-Up of Borderline Ovarian Tumors

    PubMed Central

    Zikan, Michal; Dundr, Pavel; Cibula, David

    2012-01-01

    Borderline ovarian tumors represent a heterogeneous group of noninvasive tumors of uncertain malignant potential with characteristic histology. They occur in younger women, are present at an early stage, and have a favorable prognosis, but symptomatic recurrence and death may be found as long as 20 years after therapy in some patients. The molecular changes in borderline ovarian tumors indicate linkage of this disease to type I ovarian tumors (low-grade ovarian carcinomas). The pathological stage of disease and subclassification of extraovarian disease into invasive and noninvasive implants, together with the presence of postoperative macroscopic residual disease, appear to be the major predictor of recurrence and survival. However, it should be emphasized that the most important negative prognostic factor for recurrence is just the use of conservative surgery, but without any impact on patient survival because most recurrent diseases are of the borderline type—easily curable and with an excellent prognosis. Borderline tumors are difficult masses to correctly preoperatively diagnose using imaging methods because their macroscopic features may overlap with invasive and benign ovarian tumors. Over the past several decades, surgical therapy has shifted from a radical approach to more conservative treatment; however, oncologic safety must always be balanced. Follow-up is essential using routine ultrasound imaging, with special attention paid to the remaining ovary in conservatively treated patients. Current literature on this topic leads to a number of controversies that will be discussed thoroughly in this article, with the aim to provide recommendations for the clinical management of these patients. PMID:23024155

  11. The mannose receptor LY75 (DEC205/CD205) modulates cellular phenotype and metastatic potential of ovarian cancer cells.

    PubMed

    Faddaoui, Adnen; Bachvarova, Magdalena; Plante, Marie; Gregoire, Jean; Renaud, Marie-Claude; Sebastianelli, Alexandra; Gobeil, Stephane; Morin, Chantale; Macdonald, Elizabeth; Vanderhyden, Barbara; Bachvarov, Dimcho

    2016-03-22

    The molecular basis of epithelial ovarian cancer (EOC) dissemination is still poorly understood. Previously, we identified the mannose receptor LY75 gene as hypomethylated in high-grade (HG) serous EOC tumors, compared to normal ovarian tissues. LY75 represents endocytic receptor expressed on dendritic cells and so far, has been primarily studied for its role in antigen processing and presentation. Here we demonstrate that LY75 is overexpressed in advanced EOC and that LY75 suppression induces mesenchymal-to-epithelial transition (MET) in EOC cell lines with mesenchymal morphology (SKOV3 and TOV112), accompanied by reduction of their migratory and invasive capacity in vitro and enhanced tumor cell colonization and metastatic growth in vivo. LY75 knockdown in SKOV3 cells also resulted in predominant upregulation of functional pathways implicated in cell proliferation and metabolism, while pathways associated with cell signaling and adhesion, complement activation and immune response were mostly suppressed. Moreover, LY75 suppression had an opposite effect on EOC cell lines with epithelial phenotype (A2780s and OV2008), by directing epithelial-to-mesenchymal transition (EMT) associated with reduced capacity for in vivo EOC cell colonization, as similar/identical signaling pathways were reversely regulated, when compared to mesenchymal LY75 knockdown EOC cells.To our knowledge, this is the first report of a gene displaying such pleiotropic effects in sustaining the cellular phenotype of EOC cells and points to novel functions of this receptor in modulating EOC dissemination. Our data also support previous findings regarding the superior capacity of epithelial cancer cells in metastatic colonization of distant sites, compared to cancer cells with mesenchymal-like morphology. PMID:26871602

  12. The mannose receptor LY75 (DEC205/CD205) modulates cellular phenotype and metastatic potential of ovarian cancer cells

    PubMed Central

    Faddaoui, Adnen; Bachvarova, Magdalena; Plante, Marie; Gregoire, Jean; Renaud, Marie-Claude; Sebastianelli, Alexandra; Gobeil, Stephane; Morin, Chantale; Macdonald, Elizabeth; Vanderhyden, Barbara; Bachvarov, Dimcho

    2016-01-01

    The molecular basis of epithelial ovarian cancer (EOC) dissemination is still poorly understood. Previously, we identified the mannose receptor LY75 gene as hypomethylated in high-grade (HG) serous EOC tumors, compared to normal ovarian tissues. LY75 represents endocytic receptor expressed on dendritic cells and so far, has been primarily studied for its role in antigen processing and presentation. Here we demonstrate that LY75 is overexpressed in advanced EOC and that LY75 suppression induces mesenchymal-to-epithelial transition (MET) in EOC cell lines with mesenchymal morphology (SKOV3 and TOV112), accompanied by reduction of their migratory and invasive capacity in vitro and enhanced tumor cell colonization and metastatic growth in vivo. LY75 knockdown in SKOV3 cells also resulted in predominant upregulation of functional pathways implicated in cell proliferation and metabolism, while pathways associated with cell signaling and adhesion, complement activation and immune response were mostly suppressed. Moreover, LY75 suppression had an opposite effect on EOC cell lines with epithelial phenotype (A2780s and OV2008), by directing epithelial-to-mesenchymal transition (EMT) associated with reduced capacity for in vivo EOC cell colonization, as similar/identical signaling pathways were reversely regulated, when compared to mesenchymal LY75 knockdown EOC cells. To our knowledge, this is the first report of a gene displaying such pleiotropic effects in sustaining the cellular phenotype of EOC cells and points to novel functions of this receptor in modulating EOC dissemination. Our data also support previous findings regarding the superior capacity of epithelial cancer cells in metastatic colonization of distant sites, compared to cancer cells with mesenchymal-like morphology. PMID:26871602

  13. Ovarian mucinous tumor with malignant mural nodules: dedifferentiation or collision?

    PubMed

    Desouki, Mohamed M; Khabele, Dineo; Crispens, Marta A; Fadare, Oluwole

    2015-01-01

    Ovarian mucinous tumors with mural nodules are rare surface epithelial-stromal tumors. The mural nodules are divergent neoplasms that may be benign or malignant. The latter may be in the form of a sarcoma, carcinosarcoma, anaplastic carcinoma, or a variety of other recognized histotypes of carcinoma, which raises the question of whether malignant mural nodules represent a form of dedifferentiation in ovarian mucinous tumors or whether they represent collision tumors. We recently reported the K-RAS gene mutation status in a case of ovarian mucinous adenocarcinoma with mural nodule of high-grade sarcoma. The mucinous and sarcomatous components revealed a mutation in codon 12 of the K-RAS gene of a different nucleotide substitution, indicating that these 2 tumor components were different clones of the same tumor. Herein, we are reporting another case of a 20-yr-old woman who presented with 22 cm pelvic mass, omental caking, and ascites. A diagnosis of invasive mucinous carcinoma with mural nodules of anaplastic carcinoma was rendered. K-RAS gene mutation studies revealed p.G12V, c.35G>T mutation in the 2 components of the tumor, which is the most common mutation reported in mucinous tumors of the ovary. The fact that sarcomatous or anaplastic carcinomatous mural nodules in ovarian mucinous tumors display the same K-RAS mutations as their underlying mucinous neoplasms provides supportive evidence that at least some malignant mural nodules represent a form of dedifferentiation in ovarian mucinous tumors, rather than a collision of 2 divergent tumor types. PMID:25473748

  14. Robotic surgery for rectosigmoid junction tumor with ovarian metastases

    PubMed Central

    Bedirli, Abdulkadir; Salman, Bulent

    2015-01-01

    Isolated ovarian metastases from colorectal cancer (CRC) are rare disease presenting in approximately 3% of all patients undergoing colorectal resection. Most reports describe an open approach to the disease, but we report a case isolated ovarian metastases from CRC managed completely by robotic technique. A 54-year-old female, with a family history of CRC, was admitted for rectosigmoid junction cancer. Computed tomography scan demonstrated in rectosigmoid tumor and pelvic mass, presumed as teratoma. Robotic surgery discovered a 10-cm encapsulated tumor, attached to the left ovary, with no macroscopic peritoneal involvement. The pathologic diagnosis of the resected pelvic mass, ovarian metastases from CRC. Robotic anterior resection was performed. Operative time was lasted 165 min, considering 25 min for robotic system set up. This is the first report to describe robot-assisted anterior resection and oophorectomy in patient with isolated ovarian metastases from rectosigmoid junction cancer. PMID:25598608

  15. Early and multiple origins of metastatic lineages within primary tumors.

    PubMed

    Zhao, Zi-Ming; Zhao, Bixiao; Bai, Yalai; Iamarino, Atila; Gaffney, Stephen G; Schlessinger, Joseph; Lifton, Richard P; Rimm, David L; Townsend, Jeffrey P

    2016-02-23

    Many aspects of the evolutionary process of tumorigenesis that are fundamental to cancer biology and targeted treatment have been challenging to reveal, such as the divergence times and genetic clonality of metastatic lineages. To address these challenges, we performed tumor phylogenetics using molecular evolutionary models, reconstructed ancestral states of somatic mutations, and inferred cancer chronograms to yield three conclusions. First, in contrast to a linear model of cancer progression, metastases can originate from divergent lineages within primary tumors. Evolved genetic changes in cancer lineages likely affect only the proclivity toward metastasis. Single genetic changes are unlikely to be necessary or sufficient for metastasis. Second, metastatic lineages can arise early in tumor development, sometimes long before diagnosis. The early genetic divergence of some metastatic lineages directs attention toward research on driver genes that are mutated early in cancer evolution. Last, the temporal order of occurrence of driver mutations can be inferred from phylogenetic analysis of cancer chronograms, guiding development of targeted therapeutics effective against primary tumors and metastases. PMID:26858460

  16. Endoprosthetic proximal femur replacement: metastatic versus primary tumors.

    PubMed

    Potter, Benjamin K; Chow, Vincent E; Adams, Sheila C; Letson, G Douglas; Temple, H Thomas

    2009-12-01

    Few studies have examined the impact of underlying diagnosis on the functional and oncologic outcomes following endoprosthetic proximal femur replacement (PFR). We performed a retrospective review of 61 consecutive cemented bipolar PFR in 59 patients for treatment neoplastic lesions with a minimum follow-up of 24 months. Twenty-two patients had primary bone tumors and 39 had metastatic disease. Average follow-up for the 30 surviving patients was 55.4 months and the mean postoperative survival for the 29 patients who died was 12.2 months. Patients with primary tumors demonstrated significantly better functional outcomes than those with metastatic disease, with mean Musculoskeletal Tumor Society functional scores of 80.2 and 66.8%, respectively (p=0.0002). Age correlated inversely with functional scores (r=-0.48; p=0.0002), while femoral resection length did not. Preoperative pathologic fracture did not appear to adversely impact final functional outcomes. The Kaplan-Meier 5-year implant survival estimate was 92.5%, with aseptic loosening as the endpoint. Both functional results and survival are increased for primary tumors versus metastatic disease following PFR. However, PFR results in excellent local disease control, reliable pain relief and good functional results in both groups, with prosthesis survival exceeding that of the patient in many cases. PMID:18835153

  17. Carcinoembryonic antigen-related cell adhesion molecule 1 is expressed and as a function histotype in ovarian tumors.

    PubMed

    Li, Ning; Yang, Jing-Yan; Wang, Xiao-Ying; Wang, Hai-Tao; Guan, Bing-Xin; Zhou, Cheng-Jun

    2016-02-01

    Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a cell-cell adhesion receptor and is implicated in several cellular functions. It is rarely reported in ovarian tumors. The aim of this study is to determine the expression of CEACAM1 in ovarian tumors, trying to see whether CEACAM1 has different expression patterns as a function of histotype. Antigen expression was examined by immunohistochemistry with mouse anti-human antibody for CEACAM1. Immunohistochemistry was performed using avidin-biotin-diaminobenzide staining. The results were expressed as average score ± SD (0, negative; 8, highest) for each histotype. In ovarian tumors, the benign serous and mucinous cystadenoma negatively or weakly expressed CEACAM1, the malignant epithelial tumors strongly expressed CEACAM1, and there was significant difference between benign epithelial tumor and adenocarcinoma (P < .05). The well-differentiated serous adenocarcinoma expressed CEACAM1 mainly with membrane pattern, and the intermediately and poorly differentiated serous adenocarcinomas expressed CEACAM1 mainly with cytoplasmic pattern (P < .05). In addition, CEACAM1 expression is elevated in solid tumors of ovary but variable as a function of histotype. Compared with membranous expression, the cytoplasmic expression was observed almost in metastatic carcinoma that might decrease the adhesive interactions of the carcinoma cells with the surrounding cells, especially with tumor cells, and this could facilitate the tumor cells to metastasize to distant regions. So, we thought that cytoplasmic CEACAM1 might play an important role in tumor progression, especially in tumor metastasis. PMID:26653024

  18. Characterization of Ascites-Derived Ovarian Tumor Cells from Spontaneously Occurring Ovarian Tumors of the Chicken: Evidence for E-Cadherin Upregulation

    PubMed Central

    Tiwari, Anupama; Hadley, Jill A.; Hendricks, Gilbert L.; Elkin, Robert G.; Cooper, Timothy; Ramachandran, Ramesh

    2013-01-01

    Ovarian cancer, a highly metastatic disease, is the fifth leading cause of cancer-related deaths in women. Chickens are widely used as a model for human ovarian cancer as they spontaneously develop epithelial ovarian tumors similar to humans. The cellular and molecular biology of chicken ovarian cancer (COVCAR) cells, however, have not been studied. Our objectives were to culture COVCAR cells and to characterize their invasiveness and expression of genes and proteins associated with ovarian cancer. COVCAR cell lines (n = 13) were successfully maintained in culture for up to19 passages, cryopreserved and found to be viable upon thawing and replating. E-cadherin, cytokeratin and α-smooth muscle actin were localized in COVCAR cells by immunostaining. COVCAR cells were found to be invasive in extracellular matrix and exhibited anchorage-independent growth forming colonies, acini and tube-like structures in soft agar. Using RT-PCR, COVCAR cells were found to express E-cadherin, N-cadherin, cytokeratin, vimentin, mesothelin, EpCAM, steroidogenic enzymes/proteins, inhibin subunits-α, βA, βB, anti-müllerian hormone, estrogen receptor [ER]-α, ER-β, progesterone receptor, androgen receptor, and activin receptors. Quantitative PCR analysis revealed greater N-cadherin, vimentin, and VEGF mRNA levels and lesser cytokeratin mRNA levels in COVCAR cells as compared with normal ovarian surface epithelial (NOSE) cells, which was suggestive of epithelial-mesenchymal transformation. Western blotting analyses revealed significantly greater E-cadherin levels in COVCAR cell lines compared with NOSE cells. Furthermore, cancerous ovaries and COVCAR cell lines expressed higher levels of an E-cadherin cleavage product when compared to normal ovaries and NOSE cells, respectively. Cancerous ovaries were found to express significantly higher ovalbumin levels whereas COVCAR cell lines did not express ovalbumin thus suggesting that the latter did not originate from oviduct. Taken

  19. Characterization of ascites-derived ovarian tumor cells from spontaneously occurring ovarian tumors of the chicken: evidence for E-cadherin upregulation.

    PubMed

    Tiwari, Anupama; Hadley, Jill A; Hendricks, Gilbert L; Elkin, Robert G; Cooper, Timothy; Ramachandran, Ramesh

    2013-01-01

    Ovarian cancer, a highly metastatic disease, is the fifth leading cause of cancer-related deaths in women. Chickens are widely used as a model for human ovarian cancer as they spontaneously develop epithelial ovarian tumors similar to humans. The cellular and molecular biology of chicken ovarian cancer (COVCAR) cells, however, have not been studied. Our objectives were to culture COVCAR cells and to characterize their invasiveness and expression of genes and proteins associated with ovarian cancer. COVCAR cell lines (n = 13) were successfully maintained in culture for up to19 passages, cryopreserved and found to be viable upon thawing and replating. E-cadherin, cytokeratin and α-smooth muscle actin were localized in COVCAR cells by immunostaining. COVCAR cells were found to be invasive in extracellular matrix and exhibited anchorage-independent growth forming colonies, acini and tube-like structures in soft agar. Using RT-PCR, COVCAR cells were found to express E-cadherin, N-cadherin, cytokeratin, vimentin, mesothelin, EpCAM, steroidogenic enzymes/proteins, inhibin subunits-α, βA, βB, anti-müllerian hormone, estrogen receptor [ER]-α, ER-β, progesterone receptor, androgen receptor, and activin receptors. Quantitative PCR analysis revealed greater N-cadherin, vimentin, and VEGF mRNA levels and lesser cytokeratin mRNA levels in COVCAR cells as compared with normal ovarian surface epithelial (NOSE) cells, which was suggestive of epithelial-mesenchymal transformation. Western blotting analyses revealed significantly greater E-cadherin levels in COVCAR cell lines compared with NOSE cells. Furthermore, cancerous ovaries and COVCAR cell lines expressed higher levels of an E-cadherin cleavage product when compared to normal ovaries and NOSE cells, respectively. Cancerous ovaries were found to express significantly higher ovalbumin levels whereas COVCAR cell lines did not express ovalbumin thus suggesting that the latter did not originate from oviduct. Taken

  20. Metastatic dissemination of human ovarian epithelial carcinoma is promoted by alpha2beta1-integrin-mediated interaction with type I collagen.

    PubMed

    Fishman, D A; Kearns, A; Chilukuri, K; Bafetti, L M; O'Toole, E A; Georgacopoulos, J; Ravosa, M J; Stack, M S

    1998-01-01

    Metastatic dissemination of epithelial ovarian carcinoma is thought to be mediated via tumor cell exfoliation into the peritoneal cavity, followed by adhesion to and invasion through the mesothelium which overlies the contents of the peritoneal cavity. In this study, we have utilized short-term primary cultures to analyze the effect of specific extracellular matrix proteins on properties of human ovarian epithelial carcinoma cells which contribute to the invasive phenotype. Analysis of cell:matrix adhesive profiles indicated that ovarian carcinoma cells adhere preferentially to type I collagen. Immunoprecipitation analyses demonstrated the presence of the collagen-binding alpha2beta1 integrin in biotin-labeled ovarian carcinoma cell membranes, and cellular adhesion was inhibited by blocking antibodies directed against the alpha2 and beta1 integrin subunits. The alpha2beta1-binding peptide Asp-Gly-Glu-Ala (DGEA) was also moderately effective at blocking adhesion to collagen relative to the control peptide Ala-Gly-Glu-Ala (AGEA). Analysis of cell motility on protein-coated colloidal gold coverslips demonstrated that ovarian carcinoma cells migrate preferentially on type I collagen coated surfaces. Type I collagen promoted migration in a concentration-dependent, saturable manner, with maximal migration observed at a collagen-coating concentration of 50 microg/ml. Migration on collagen was inhibited by antibodies directed against the alpha2 and beta1 integrin subunits and by DGEA peptide, providing evidence for the role of the alpha2beta1 integrin in ovarian carcinoma cell motility. Culturing ovarian carcinoma cells on type I collagen gels led to a significant increase in conversion of the matrix metalloproteinase 2 zymogen to the 66-kD form, suggesting that adhesion to collagen also influences matrix-degrading proteinases. These data suggest that alpha2beta1-integrin-mediated interaction of ovarian carcinoma cells with type I collagen, a protein prevalent both in the

  1. Pulmonary Metastatic Choriocarcinoma from a Burned-out Testicular Tumor.

    PubMed

    Nakazaki, Hirofumi; Tokuyasu, Hirokazu; Takemoto, Yu; Miura, Hiroshi; Yanai, Masaaki; Fukushima, Takehito; Shimizu, Eiji

    2016-01-01

    A 54-year-old man was referred to our hospital because of progressive dyspnea. Chest computed tomography showed multiple nodular shadows with a peripheral ground-glass halo. His clinical condition continued to deteriorate with the development of progressive respiratory failure requiring mechanical ventilation. A histological examination of a transbronchial lung biopsy revealed choriocarcinoma. The patient died within nine days of admission. A histological examination of the right testis during an autopsy revealed a burned-out testicular tumor consisting of a teratoma and a fibrous scar. We herein report a rare case of pulmonary multiple metastatic choriocarcinoma originating from a burned-out testicular tumor. PMID:27250057

  2. Endosalpingiosis in Conjunction with Ovarian Serous Cystadenoma Mimicking Metastatic Ovarian Malignancy

    PubMed Central

    Singhania, Namrata; Janakiraman, Neha; Coslett, Douglas; Ahmad, Navid

    2014-01-01

    Patient: Female, 26 Final Diagnosis: Endosalpingiosis Symptoms: Chronic pelvic pain Medication: — Clinical Procedure: Diagnostic laproscopy (conservative management) Specialty: Obstetrics and Gynecology Objective: Challenging differential diagnosis Background: Interesting and unusual case of endosalpingiosis mimicking ovarian malignancy presentation. Case Report: A 26-year-old G0P0 white female presented to our office with chronic pelvic pain. On vaginal examination, a nontender mass in left the adnexal region was palpable. Transvaginal ultrasound showed a left ovarian cyst. Laparoscopy was performed, which revealed diffuse bilateral ovarian excrescences with unusual multiple studdings throughout the peritoneum and abdominal cavity. Due to a suspicion of malignancy, a biopsy specimen was obtained for frozen sectioning. The specimen proved to be consistent with benign papillary serous cystadenofibroma. Gross appearance was still suspicious for malignancy and therefore left paraovarian cystectomy was performed. Additional specimens showed ovarian adenofibroma and endosalpingiosis. The patient’s complaint of pelvic pain improved after laparoscopy. Due to diffuse presentation of endosalpingiosis in the peritoneum, serial CT scan of abdomen and pelvis at 6-month intervals was recommended. Conclusions: To our knowledge, this is an unusual case of a young, nulliparous female presenting with diffuse-presentation endosalpingiosis in the abdomen and peritoneum, which on gross examination was suspicious for malignancy. By following a conservative approach and performing serial CT scans, the patient will be clinically monitored. PMID:25180540

  3. Bone marrow as a metastatic niche for disseminated tumor cells from solid tumors

    PubMed Central

    Shiozawa, Yusuke; Eber, Matthew R; Berry, Janice E; Taichman, Russell S

    2015-01-01

    Bone marrow is a heterogeneous organ containing diverse cell types, and it is a preferred metastatic site for several solid tumors such as breast and prostate cancer. Recently, it has been shown that bone metastatic cancer cells interact with the bone marrow microenvironment to survive and grow, and thus this microenvironment is referred to as the ‘metastatic niche'. Once cancer cells spread to distant organs such as bone, the prognosis for the patient is generally poor. There is an urgent need to establish a greater understanding of the mechanisms whereby the bone marrow niche influences bone metastasis. Here we discuss insights into the contribution of the bone marrow ‘metastatic niche' to progression of bone metastatic disease, with a particular focus on cells of hematopoietic and mesenchymal origin. PMID:26029360

  4. Large malignant ovarian tumors during pregnancy: two cases

    PubMed Central

    Xu, Dong; Liang, Cheng; He, Jing

    2014-01-01

    The present study reports two cases of large ovarian malignancy during pregnancy, which is very rare. The two patients were received between Nov 2012 and Feb 2013 at Gynecological and Obstetrical Department, Women’s Hospital, School of Medicine, Zhejiang University (People’s Republic of China). Both cases present tumor sized more than 20 cm, with one case of 40 cm. Both patients underwent timely cesarean section, with survival of the Child, and successful removal of the tumor. All patients showed good outcome in the follow-up period. Therefore the large ovarian malignancy during pregnancy could be well treated after careful clinical evaluation. PMID:25484595

  5. Ovarian Tumor Cells Studied Aboard the International Space Station (ISS)

    NASA Technical Reports Server (NTRS)

    2001-01-01

    In August 2001, principal investigator Jeanne Becker sent human ovarian tumor cells to the International Space Station (ISS) aboard the STS-105 mission. The tumor cells were cultured in microgravity for a 14 day growth period and were analyzed for changes in the rate of cell growth and synthesis of associated proteins. In addition, they were evaluated for the expression of several proteins that are the products of oncogenes, which cause the transformation of normal cells into cancer cells. This photo, which was taken by astronaut Frank Culbertson who conducted the experiment for Dr. Becker, shows two cell culture bags containing LN1 ovarian carcinoma cell cultures.

  6. Autoantibodies targeting tumor-associated antigens in metastatic cancer

    PubMed Central

    Oaks, Martin; Taylor, Samuel; Shaffer, James

    2013-01-01

    In addition to the well-established effector functions of IgGs, including direct cytotoxicity and antibody-dependent cellular cytotoxicity, some populations of IgGs may exert anti-inflammatory effects. Here, we describe a population of antibodies that form in the natural course of metastatic cancer and contain glycans that terminate with sialic acid. We demonstrate that both the titer of these antibodies and their level of sialylation are relatively stable throughout the progression of metastatic melanoma. The sialylation pattern of these antibodies somehow correlates with their specificity for tumor-associated antigens, as IgGs targeting several antigens associated with infectious agents are relatively poor of sialic acid. We also show that some antibodies targeting the melanoma-associated antigen NY-ESO-1 bind to the human C-type lectin CD209 (DC-SIGN). We propose that these antibodies are candidate anti-inflammatory antibodies. The presence of anti-inflammatory antibodies in cancer patients may explain, at least in part, why tumors persist and spread in the host despite strong tumor-specific humoral responses. The elucidation of the cellular and molecular pathways involved in the induction of anti-inflammatory antibodies specific for tumor-associated antigens and their function may yield important insights into how tumors evade immune detection and progress. PMID:23894724

  7. Metastatic tumors to the stomach: Clinical and endoscopic features

    PubMed Central

    Palma, Giovanni D De; Masone, Stefania; Rega, Maria; Simeoli, Immacolata; Donisi, Mario; Addeo, Pietro; Iannone, Loredana; Pilone, Vincenzo; Persico, Giovanni

    2006-01-01

    AIM: To evaluate the clinical and endoscopic patterns in a large series of patients with metastatic tumors in the stomach. METHODS: A total of 64 patients with gastric meta-stases from solid malignant tumors were retros-pectively examined between 1990 and 2005. The clinicopathological findings were reviewed along with tumor characteristics such as endoscopic pattern, location, size and origin of the primary sites. RESULTS: Common indications for endoscopy were anemia, bleeding and epigastric pain. Metastases presented as solitary (62.5%) or multiple (37.5%) tumors were mainly located in the middle or upper third of stomach. The main primary metastatic tumors were from breast and lung cancer and malignant melanoma. CONCLUSION: As the prognosis of cancer patients has been improving gradually, gastrointestinal (GI) metastases will be encountered more often. Endoscopic examinations should be conducted carefully in patients with malignancies, and endoscopic biopsies and information on the patient’s clinical history are useful for correct diagnosis of gastric metastases. PMID:17143949

  8. A nanoparticle formulation that selectively transfects metastatic tumors in mice

    PubMed Central

    Yang, Jian; Hendricks, William; Liu, Guosheng; McCaffery, J. Michael; Kinzler, Kenneth W.; Huso, David L.; Vogelstein, Bert; Zhou, Shibin

    2013-01-01

    Nanoparticle gene therapy holds great promise for the treatment of malignant disease in light of the large number of potent, tumor-specific therapeutic payloads potentially available for delivery. To be effective, gene therapy vehicles must be able to deliver their therapeutic payloads to metastatic lesions after systemic administration. Here we describe nanoparticles comprised of a core of high molecular weight linear polyethylenimine (LPEI) complexed with DNA and surrounded by a shell of polyethyleneglycol-modified (PEGylated) low molecular weight LPEI. Compared with a state-of-the-art commercially available in vivo gene delivery formulation, i.v. delivery of the core/PEGylated shell (CPS) nanoparticles provided more than a 16,000-fold increase in the ratio of tumor to nontumor transfection. The vast majority of examined liver and lung metastases derived from a colorectal cancer cell line showed transgene expression after i.v. CPS injection in an animal model of metastasis. Histological examination of tissues from transfected mice revealed that the CPS nanoparticles selectively transfected neoplastic cells rather than stromal cells within primary and metastatic tumors. However, only a small fraction of neoplastic cells (<1%) expressed the transgene, and the extent of delivery varied with the tumor cell line, tumor site, and host mouse strain used. Our results demonstrate that these CPS nanoparticles offer substantial advantages over previously described formulations for in vivo nanoparticle gene therapeutics. At the same time, they illustrate that major increases in the effectiveness of such approaches are needed for utility in patients with metastatic cancer. PMID:23959886

  9. Autoantibodies to tumor-associated antigens in epithelial ovarian carcinoma.

    PubMed

    Piura, Benjamin; Piura, Ettie

    2009-01-01

    This review will focus on recent knowledge related to circulating autoantibodies (AAbs) to tumor-associated antigens (TAAs) in epithelial ovarian carcinoma. So far, the following TAAs have been identified to elicit circulating AAbs in epithelial ovarian carcinoma: p53, homeobox proteins (HOXA7, HOXB7), heat shock proteins (HSP-27, HSP-90), cathepsin D, cancer-testis antigens (NY-ESO-1/LAGE-1), MUC1, GIPC-1, IL-8, Ep-CAM, and S100A7. Since AAbs to TAAs have been identified in the circulation of patients with early-stage cancer, it has been speculated that the assessment of a panel of AAbs specific for epithelial ovarian carcinoma TAAs might hold great potential as a novel tool for early diagnosis of epithelial ovarian carcinoma. PMID:20145720

  10. Metastatic breast cancer: ovarian ablation with lower half-body irradiation

    SciTech Connect

    Fitzpatrick, P.J.; Garrett, P.G.

    1981-11-01

    Lower half-body irradiation with 1000 rad in a single exposure was used to treat 34 pre- and perimenopausal women with metastatic breast cancer. A direct response with relief of pain in the treated area occurred in 21 of 26 (82%) assessable patients. An indirect response in distant metastases was seen in 9 of 28 (32%) patients as a result of ovarian ablation. The median duration for both responses was 17 months. Treatment was well tolerated and no late complictions developed. Subsequent therapy for progressive cancer, with either radiation, hormones or chemotherapy was not compromised by this approach.

  11. Ovarian yolk sac tumors in older women arising from epithelial ovarian tumors or with no detectable epithelial component.

    PubMed

    Roth, Lawrence M; Talerman, Aleksander; Levy, Tally; Sukmanov, Oleg; Czernobilsky, Bernard

    2011-09-01

    Yolk sac tumor (YST) occurs rarely in older women, either in association with a variety of ovarian epithelial tumors or, considerably less often, without an identifiable epithelial precursor. The patients often have elevated serum levels of α-fetoprotein that roughly correlate with the amount of the YST component. In postmenopausal women with an ovarian mass and elevated serum levels of α-fetoprotein, a tumor of this type should be suspected. Endometrioid carcinoma is the most common putative precursor, and the tumor is often associated with an endometriotic cyst; however, malignant Müllerian mixed tumor and mucinous neoplasms have also been reported as precursors. We report 4 cases of YST in postmenopausal women. Of the 3 cases with an identified epithelial component, 1 was serous carcinoma, another was clear cell adenocarcinoma, and the third was an admixture of endometrioid and clear cell adenocarcinoma arising from an endometriotic cyst. Although a precursor epithelial ovarian neoplasm, typically a malignancy (somatic carcinoma), is usually identified, no precursor neoplasm was observed in 1 of our cases and in 5 cases from the literature. We believe that YSTs in older women, whether or not an epithelial component is detected histologically, constitute a single entity that is distinct from YSTs in younger patients and should be treated aggressively. Neoplasms with a YST component in older women are less responsive to the chemotherapy currently used for ovarian germ cell tumors; therefore, adjuvant therapy should include platinum-based chemotherapy designed to treat both epithelial ovarian cancer and germ cell tumors. Of the 24 reported cases, including our own, 17 died of neoplasms within 25 months and another was living with disease at 2 months. However, 2 more recent patients treated aggressively with platinum-based chemotherapy designed to treat both epithelial and germ cell tumor components with stage 1 disease are living and have been disease free >1

  12. Cannibalism: a way to feed on metastatic tumors.

    PubMed

    Fais, Stefano

    2007-12-18

    Cannibalism of tumors is an old story for pathologists, but it remained a mystery for at least one century. Recent data highlighted tumor cannibalism as a key advantage in tumor malignancy, possibly involved in resistance of tumors to the specific immune reaction. However, new data suggests also that metastatic tumor cells may use this peculiar function to feed in conditions of low nutrient supply. This makes malignant cancer cells more similar to microorganisms, rather than to normal cells undergoing malignant transformation. In cytological or histological samples of human tumors it is common to detect cells with one or many vacuoles, possibly containing cells under degradation, that push the nucleus to the periphery giving it the shape of a crescent moon. The cannibal cells may feed on sibling tumor cells, but also of the lymphocytes that should kill them. Cannibal cells eat everything without distinguishing between the feeding materials, with a mechanism that mostly differ from typical phagocytosis. Despite such phenomenon is considered mainly non-selective, a molecular framework of factors that contribute to cannibalism has been described. This machinery includes the presence of an acidic environment that allows a continuous activation of specific lytic enzymes, such as cathepsin B. Cannibalism occurs in apparently well defined structures whose main actors are big caveolar-like vacuoles and a connection between caveolin-1 and the actin cytoskeleton through the actin-linker molecule ezrin. Each of the components of the cannibal framework may represent specific tumor targets for future new strategies against cancer. PMID:17977647

  13. Clodronate inhibits tumor angiogenesis in mouse models of ovarian cancer

    PubMed Central

    Reusser, Nicole M; Dalton, Heather J; Pradeep, Sunila; Gonzalez-Villasana, Vianey; Jennings, Nicholas B; Vasquez, Hernan G; Wen, Yunfei; Rupaimoole, Rajesh; Nagaraja, Archana S; Gharpure, Kshipra; Miyake, Takahito; Huang, Jie; Hu, Wei; Lopez-Berestein, Gabriel; Sood, Anil K

    2014-01-01

    Purpose Bisphosphonates have been shown to inhibit and deplete macrophages. The effects of bisphosphonates on other cell types in the tumor microenvironment have been insufficiently studied. Here, we sought to determine the effects of bisphosphonates on ovarian cancer angiogenesis and growth via their effect on the microenvironment, including macrophage, endothelial and tumor cell populations. Experimental Design Using in vitro and in vivo models, we examined the effects of clodronate on angiogenesis and macrophage density, and the overall effect of clodronate on tumor size and metastasis. Results Clodronate inhibited the secretion of pro-angiogenic cytokines by endothelial cells and macrophages, and decreased endothelial migration and capillary tube formation. In treated mice, clodronate significantly decreased tumor size, number of tumor nodules, number of tumor-associated macrophages and tumor capillary density. Conclusions Clodronate is a potent inhibitor of tumor angiogenesis. These results highlight clodronate as a potential therapeutic for cancer. PMID:24841852

  14. Sonographic findings of an ovarian serous surface papillary borderline tumor.

    PubMed

    Kwon, Yohan; Park, Sung Bin; Lee, Jong Beum; Park, Hyun Jeong

    2013-01-01

    Sonographic findings of a serous surface papillary borderline tumor of the ovary have rarely been reported in the English literature. Here, we describe a case of serous surface papillary borderline tumor, which was depicted on gray-scale and Doppler ultrasonography as smoothly lobulated and polypoid heterogeneous echoic bilateral adnexal masses encased or surrounded by what was presumed to be normal-appearing ovarian follicles with increased vascular flow. PMID:23938140

  15. Clinicopathologic features of ovarian Sertoli-Leydig cell tumors

    PubMed Central

    Zhang, Hai-Yan; Zhu, Jia-Er; Huang, Wen; Zhu, Jin

    2014-01-01

    Background: Ovarian Stertoli-Ledig cell tumor (SLCT) is a rare type of sex cord-stromal tumor of the ovary. The present study was to evaluate clinicalopahologic features and prognosis of patients with Sertoli-Leydig cell tumor treated by surgery and adjuvant chemotherapy during short term follow-up. Methods: A total of sixteen patients with ovarian Sertoli-Leydig cell tumor treated at the Obstetrics and Gynecology Hospital, Shanghai, China, between Jan 2001 and Dec 2011 were reviewed. The clinical data, treatment and prognosis were obtained from medical records. Results: The median age of the patients with ovarian Sertoli-Leydig cell tumor was about 27.5 years old in non-menopausal women, while the median age of menopausal women was about 63 years old. The most common complaint was with hormonal-related symptoms in the form of secondary amenorrhea and infinity, features of virilization, abdominal mass or irregular vaginal bleeding. All of sixteen patients underwent surgical staging and all were found to have stage I disease at the time of diagnosis. Eleven patients with intermediate and two patients with poorly differentiated tumors received adjuvant chemotherapy. There were differences found in operative time, blood loss and postoperative recovery time between laparotomy and laparoscopy. There were no disease-related deaths and all patients were under complete remission at the last follow-up. Conclusions: Ovarian Sertoli-Leydig cell tumors could happen in any period age of women. However, the tumors typically occur in the single side while still at the early stage, a favorable outcome could be achieved by surgery and adjuvant chemotherapy. Laparoscopy has similar surgical effects as laparotomy, but has a number of advantages. PMID:25400781

  16. Detection of Human Papillomavirus-16 E6-Oncoprotein in Epithelial Ovarian Tumors Samples of Iraqi Patients

    PubMed Central

    Mahmood, Fahem Mohsin; Kadhim, Haider Sabah; Mousa Al Khuzaee, Liqaa Riadh

    2014-01-01

    Background: Human papillomavirus (HPV) is the causal factor for cervical cancer. However, the role of HPV infection in ovarian cancer is unclear. Objectives: This study aimed to determine the presence of human papillomavirus-16 (HPV-16) in ovarian tumor tissues. Patients and Methods: This was a retrospective study, which included 61 Archived human ovarian tumor tissues embedded in paraffin blocks. The ovarian tumor tissues were divided into four groups. The first group was the malignant ovarian epithelial tumor group; it included 31 cases with invasive surface epithelial ovarian tumors. The second group was the borderline epithelial ovarian tumor group: it included four cases with borderline intermediate malignancy. The third group was the benign epithelial ovarian tumors group: it included 18 cases with benign epithelial ovarian tumors. The fourth group had functional ovarian cystic lesions: it included eight cases with non-neoplastic functional ovarian cysts. Sections were made from each of the paraffin embedded blocks and examined using immunohistochemistry to detect HPV 16-E6-oncoprotein in ovarian tumor tissues. Results: Out of the eight cases with functional cysts only one case (12.5%) expressed HPV. No HPV expression was seen in cases with benign and borderline tumors. Out of the 31 cases with one malignant surface epithelial ovarian tumor only three (9.67%) cases expressed HPV. There was no significant statistical difference in HPV expression among neoplastic and non-neoplastic ovarian tumors included in the present study (P= 0.476). Conclusions: HPV type 16 was detected in only 9.67% of malignant epithelial tumors. It appears that HPV infection plays a relatively minor role in the pathogenesis of ovarian carcinomas. PMID:25485061

  17. Granulosa cell tumor presenting with ovarian torsion and de novo borderline mucinous ovarian tumor in the contralateral ovary.

    PubMed

    Ates, S; Sevket, O; Sudolmus, S; Sonmez, F C; Dansuk, R

    2015-01-01

    The authors report a case of 25-year-old women with a rare acute presentation of granulosa cell tumor (GCT) as an ovarian torsion. Right salpingoo-ooferectomy was performed. The pathological diagnosis was GCT One month after the surgery there was a three-cm ovarian cyst in the contralateral ovary and the tumor size increased to six cm in diameter in the following month. Serum inhibin-B levels progressively increased. Cystectomy was performed to contralateral ovary as frozen-section examination indicated mucinous tumor. Final histopathological examination revealed borderline mucinous tumor. Regarding her request, the patient was reoperated again and unilateral oophorectomy and hysterectomy were performed. Clinicians must be aware of the possibility of an underlying malignancy associated with adnexal torsion even in young patients. Frozen section will be helpful in order to avoid incomplete surgeries. Cyst rapidly growing in the ovary in young women should raise the suspicion of a de novo malignancy. PMID:26189271

  18. Dll4 Inhibition plus Aflibercept Markedly Reduces Ovarian Tumor Growth.

    PubMed

    Huang, Jie; Hu, Wei; Hu, Limin; Previs, Rebecca A; Dalton, Heather J; Yang, Xiao-Yun; Sun, Yunjie; McGuire, Michael; Rupaimoole, Rajesha; Nagaraja, Archana S; Kang, Yu; Liu, Tao; Nick, Alpa M; Jennings, Nicholas B; Coleman, Robert L; Jaffe, Robert B; Sood, Anil K

    2016-06-01

    Delta-like ligand 4 (Dll4), one of the Notch ligands, is overexpressed in ovarian cancer, especially in tumors resistant to anti-VEGF therapy. Here, we examined the biologic effects of dual anti-Dll4 and anti-VEGF therapy in ovarian cancer models. Using Dll4-Fc blockade and anti-Dll4 antibodies (murine REGN1035 and human REGN421), we evaluated the biologic effects of Dll4 inhibition combined with aflibercept or chemotherapy in orthotopic mouse models of ovarian cancer. We also examined potential mechanisms by which dual Dll4 and VEGF targeting inhibit tumor growth using immunohistochemical staining for apoptosis and proliferation markers. Reverse-phase protein arrays were used to identify potential downstream targets of Dll4 blockade. Dual targeting of VEGF and Dll4 with murine REGN1035 showed superior antitumor effects in ovarian cancer models compared with either monotherapy. In the A2780 model, REGN1035 (targets murine Dll4) or REGN421 (targets human Dll4) reduced tumor weights by 62% and 82%, respectively; aflibercept alone reduced tumor weights by 90%. Greater therapeutic effects were observed for Dll4 blockade (REGN1035) combined with either aflibercept or docetaxel (P < 0.05 for the combination vs. aflibercept). The superior antitumor effects of REGN1035 and aflibercept were related to increased apoptosis in tumor cells compared with the monotherapy. We also found that GATA3 expression was significantly increased in tumor stroma from the mice treated with REGN1035 combined with docetaxel or aflibercept, suggesting an indirect effect of these combination treatments on the tumor stroma. These findings identify that dual targeting of Dll4 and VEGF is an attractive therapeutic approach. Mol Cancer Ther; 15(6); 1344-52. ©2016 AACR. PMID:27009216

  19. Metastatic tumors in the duodenum: A report of two cases.

    PubMed

    Iwamuro, Masaya; Uetsuka, Hirokazu; Makihata, Kiyoshi; Yamamoto, Kazuhide

    2015-01-01

    Two cases are presented involving a 71-year-old male with adenocarcinoma of the lung and a 57-year-old male with adenocarcinoma of the sigmoid colon, each with metastatic lesions located in the duodenal bulb. Each lesion appeared as a submucosal tumor with an ulcer at the center. Lymph node swelling in the hepatoduodenal ligament was also found to precede the emergence of each duodenal metastasis. These cases indicate that involvement of the lymph node in the hepatoduodenal ligament may be a forerunner of duodenal metastasis. PMID:26458611

  20. Inhibition of metastatic tumor growth and metastasis via targeting metastatic breast cancer by chlorotoxin-modified liposomes.

    PubMed

    Qin, Chao; He, Bing; Dai, Wenbing; Zhang, Hua; Wang, Xueqing; Wang, Jiancheng; Zhang, Xuan; Wang, Guangji; Yin, Lifang; Zhang, Qiang

    2014-10-01

    A liposome system modified with chlorotoxin (ClTx), a scorpion venom peptide previously utilized for targeting brain tumors, was established. Its targeting efficiency and antimetastasis behavior against metastatic breast cancer highly expressed MMP-2, the receptor of ClTx, were investigated. 4T1, a metastatic breast cancer cell line derived from a murine breast tumor, was selected as the cell model. As results, the ClTx-modified liposomes displayed specific binding to 4T1 as determined by flow cytometry and confocal imaging. The cytotoxicity assay revealed that the ClTx modification increased the toxicity compared with nonmodified liposomes. In addition, the modified liposomes also exhibited high in vivo targeting efficiency in the BALB/c mice bearing 4T1 tumors. Importantly, this system inhibited the growth of metastatic tumor and prevented the incidence of lung metastasis in mice bearing 4T1 tumors with only low systemic toxicity. The data obtained from the in vitro and in vivo studies confirmed that the ClTx-modified liposomes increased the drug delivery to metastatic breast cancers. This study proved that the ClTx-modified liposomes had targeting ability to metastatic breast cancer in addition to brain cancer, and displayed an obvious antimetastasis effect. Generally, it may provide a promising strategy for metastatic breast cancer therapy. PMID:24559485

  1. Diagnostic potential of tumor DNA from ovarian cyst fluid

    PubMed Central

    Wang, Yuxuan; Sundfeldt, Karin; Mateoiu, Constantina; Shih, Ie-Ming; Kurman, Robert J; Schaefer, Joy; Silliman, Natalie; Kinde, Isaac; Springer, Simeon; Foote, Michael; Kristjansdottir, Björg; James, Nathan; Kinzler, Kenneth W; Papadopoulos, Nickolas; Diaz, Luis A; Vogelstein, Bert

    2016-01-01

    We determined whether the mutations found in ovarian cancers could be identified in the patients' ovarian cyst fluids. Tumor-specific mutations were detectable in the cyst fluids of 19 of 23 (83%) borderline tumors, 10 of 13 (77%) type I cancers, and 18 of 18 (100%) type II cancers. In contrast, no mutations were found in the cyst fluids of 18 patients with benign tumors or non-neoplastic cysts. Though large, prospective studies are needed to demonstrate the safety and clinical utility of this approach, our results suggest that the genetic evaluation of cyst fluids might be able to inform the management of the large number of women with these lesions. DOI: http://dx.doi.org/10.7554/eLife.15175.001 PMID:27421040

  2. Integrin-linked kinase activity modulates the pro-metastatic behavior of ovarian cancer cells

    PubMed Central

    Bruney, Lana; Liu, Yueying; Grisoli, Anne; Ravosa, Matthew J.; Stack, M. Sharon

    2016-01-01

    Epithelial ovarian cancer (EOC) is the most fatal gynecologic cancer in the U.S., resulting in >14,000 deaths/year. Most women are diagnosed at late stage with widely disseminated intra-peritoneal metastatic disease, resulting in a 5-year survival rate of <30%. EOCs spread via direct extension and exfoliation into the peritoneal cavity, adhesion to peritoneal mesothelial cells, mesothelial cell retraction to expose sub-mseothelial matrix and anchoring in the type I collagen-rich matrix to generate secondary lesions. As a molecular-level understanding of EOC metastasis may identify novel therapeutic targets, the current study evaluated the expression and activity of integrin-linked kinase (ILK), a Ser/Thr protein kinase activated upon integrin-mediated adhesion. Results show that ILK is co-expressed in EOC with the pro-metastatic enzyme membrane type 1 matrix metalloproteinase (MT1-MMP) and catalyzed phosphorylation of the cytoplasmic tail of the proteinase. Downregulation of ILK expression or activity reduced adhesion to and invasion of collagen gels and organotypic meso-mimetic cultures. As an initial early event in EOC metastasis is integrin-mediated adhesion, these results suggest that further evaluation of ILK inhibitors as anti-metastatic agents in EOC is warranted. PMID:26959113

  3. Early inflammatory response in epithelial ovarian tumor cyst fluids.

    PubMed

    Kristjánsdóttir, Björg; Partheen, Karolina; Fung, Eric T; Yip, Christine; Levan, Kristina; Sundfeldt, Karin

    2014-10-01

    Mortality rates for epithelial ovarian cancer (EOC) are high, mainly due to late-stage diagnosis. The identification of biomarkers for this cancer could contribute to earlier diagnosis and increased survival rates. Given that chronic inflammation plays a central role in cancer initiation and progression, we selected and tested 15 cancer-related cytokines and growth factors in 38 ovarian cyst fluid samples. We used ovarian cyst fluid since it is found in proximity to the pathology and mined it for inflammatory biomarkers suitable for early detection of EOC. Immunoprecipitation and high-throughput sample fractionation were obtained by using tandem antibody libraries bead and mass spectrometry. Two proteins, monocyte chemoattractant protein-1 (MCP-1/CCL2) and interleucin-8 (IL-8/CXCL8), were significantly (P < 0.0001) higher in the malignant (n = 16) versus benign (n = 22) tumor cysts. Validation of MCP-1, IL-8, and growth-regulated protein-α (GROα/CXCL1) was performed with ELISA in benign, borderline, and malignant cyst fluids (n = 256) and corresponding serum (n = 256). CA125 was measured in serum from all patients and used in the algorithms performed. MCP-1, IL-8, and GROα are proinflammatory cytokines and promoters of tumor growth. From 5- to 100-fold higher concentrations of MCP-1, IL-8 and GROα were detected in the cyst fluids compared to the serum. Significant (P < 0.001) cytokine response was already established in borderline cyst fluids and stage I EOC. In serum a significant (P < 0.01) increase of IL-8 and GROα was found, but not until stage I and stage III EOC, respectively. These findings confirm that early events in tumorigenesis can be analyzed and detected in the tumor environment and we conclude that ovarian cyst fluid is a promising source in the search for new biomarkers for early ovarian tumors. PMID:24947406

  4. Differentiating Metastatic and Non-metastatic Tumor Cells from Their Translocation Profile through Solid-State Micropores.

    PubMed

    Ali, Waqas; Ilyas, Azhar; Bui, Loan; Sayles, Bailey; Hur, Yeun; Kim, Young-Tae; Iqbal, Samir M

    2016-05-17

    Cancer treatment, care, and outcomes are much more effective if started at early stages of the disease. The presence of malignant cancer cells in human samples such as blood or biopsied tissue can be used to reduce overtreatment and underdiagnosis as well as for prognosis monitoring. Reliable quantification of metastatic tumor cells (MTCs) and non-metastatic tumor cells (NMTCs) from human samples can help in cancer staging as well. We report a simple, fast, and reliable approach to identify and quantify metastatic and non-metastatic cancer cells from whole biological samples in a point-of-care manner. The metastatic (MDA MB-231) and non-metastatic (MCF7) breast cancer cells were pushed through a solid-state micropore made in a 200 nm thin SiO2 membrane while measuring current across the micropore. The cells generated very distinctive translocation profiles. The translocation differences stemmed from their peculiar mechanophysical properties. The detection efficiency of the device for each type of tumor cells was ∼75%. MTCs showed faster translocation (36%) and 34% less pore blockage than NMTCs. The micropore approach is simple, exact, and quantitative for metastatic cell detection in a lab-on-a chip setting, without the need for any preprocessing of the sample. PMID:27035212

  5. Review of ovarian tumors in children and adolescents: radiologic-pathologic correlation.

    PubMed

    Heo, Suk Hee; Kim, Jin Woong; Shin, Sang Soo; Jeong, Seo In; Lim, Hyo Soon; Choi, Yoo Duk; Lee, Kyoung Hwa; Kang, Woo Dae; Jeong, Yong Yeon; Kang, Heoung Keun

    2014-01-01

    The incidence, histologic distribution, and clinical manifestations of ovarian tumors in the pediatric population are distinct from those in adults. Although ovarian neoplasms in childhood and adolescence are rare, the diagnosis should be considered in young girls with abdominal pain and a palpable mass. Differential diagnosis in children and adolescents with ovarian tumors should be conducted on the basis of unique clinical manifestations, elevated serum tumor marker levels, and distinctive imaging findings. Although the clinical manifestations are nonspecific and may overlap, they may assist in diagnosis of some types of ovarian tumors. Children who present with a palpable mass or symptoms of precocious puberty have a high likelihood of malignancy. Many ovarian tumors are associated with abnormal hormonal activity and/or abnormal sexual development. Elevated levels of serum tumor markers, including α-fetoprotein, the beta subunit of human chorionic gonadotropin, and CA-125, raise concern for ovarian malignancies. However, negative tumor markers do not exclude the possibility of malignancy. Identification of imaging features at ultrasonography, computed tomography, and magnetic resonance imaging can help differentiate benign from malignant ovarian tumors and, in turn, plays a crucial role in determining treatment options. At imaging, malignant ovarian tumors usually appear predominantly solid or heterogeneous and are larger than benign tumors. Because surgery is the primary treatment for ovarian tumors, ovarian salvage with fertility preservation and use of a minimally invasive surgical technique are important in children and adolescents. PMID:25384300

  6. Propranolol Hydrochloride in Treating Patients With Locally Recurrent or Metastatic Solid Tumors That Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2016-01-16

    Male Breast Cancer; Recurrent Melanoma; Stage IV Breast Cancer; Stage IV Melanoma; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Unspecified Adult Solid Tumor, Protocol Specific; Hepatocellular Carcinoma

  7. In vitro Enrichment of Ovarian Cancer Tumor-initiating Cells

    PubMed Central

    House, Carrie D.; Hernandez, Lidia; Annunziata, Christina M.

    2015-01-01

    Evidence suggests that small subpopulations of tumor cells maintain a unique self-renewing and differentiation capacity and may be responsible for tumor initiation and/or relapse. Clarifying the mechanisms by which these tumor-initiating cells (TICs) support tumor formation and progression could lead to the development of clinically favorable therapies. Ovarian cancer is a heterogeneous and highly recurrent disease. Recent studies suggest TICs may play an important role in disease biology. We have identified culture conditions that enrich for TICs from ovarian cancer cell lines. Growing either adherent cells or non-adherent ‘floater’ cells in a low attachment plate with serum free media in the presence of growth factors supports the propagation of ovarian cancer TICs with stem cell markers (CD133 and ALDH activity) and increased tumorigenicity without the need to physically separate the TICs from other cell types within the culture. Although the presence of floater cells is not common for all cell lines, this population of cells with innate low adherence may have high tumorigenic potential.Compared to adherent cells grown in the presence of serum, TICs readily form spheres, are significantly more tumorigenic in mice, and express putative stem cell markers. The conditions are easy to establish in a timely manner and can be used to study signaling pathways important for maintaining stem characteristics, and to identify drugs or combinations of drugs targeting TICs. The culture conditions described herein are applicable for a variety of ovarian cancer cells of epithelial origin and will be critical in providing new information about the role of TICs in tumor initiation, progression, and relapse. PMID:25742116

  8. Updates in the management of ovarian germ cell tumors.

    PubMed

    Matei, Daniela; Brown, Jubilee; Frazier, Lindsay

    2013-01-01

    Ovarian germ cell tumors are rare events at all ages-in pediatrics, adolescence, and during young adulthood. Combining the knowledge and experience of pediatric and gynecologic oncologists can lead to better outcomes for all. In this review, we intend to present the latest consensus on management of women and children with this disease and highlight the opportunities for collaboration and clinical research going forward. PMID:23714505

  9. Salt-Inducible Kinase 2 Couples Ovarian Cancer Cell Metabolism with Survival at the Adipocyte-Rich Metastatic Niche.

    PubMed

    Miranda, Fabrizio; Mannion, David; Liu, Shujuan; Zheng, Yiyan; Mangala, Lingegowda S; Redondo, Clara; Herrero-Gonzalez, Sandra; Xu, Ruoyan; Taylor, Charlotte; Chedom, Donatien Fotso; Karaminejadranjbar, Mohammad; Albukhari, Ashwag; Jiang, Dahai; Pradeep, Sunila; Rodriguez-Aguayo, Cristian; Lopez-Berestein, Gabriel; Salah, Eidarus; Abdul Azeez, Kamal R; Elkins, Jonathan M; Campo, Leticia; Myers, Kevin A; Klotz, Daniel; Bivona, Serena; Dhar, Sunanda; Bast, Robert C; Saya, Hideyuki; Choi, Hwan Geun; Gray, Nathanael S; Fischer, Roman; Kessler, Benedikt M; Yau, Christopher; Sood, Anil K; Motohara, Takeshi; Knapp, Stefan; Ahmed, Ahmed Ashour

    2016-08-01

    The adipocyte-rich microenvironment forms a niche for ovarian cancer metastasis, but the mechanisms driving this process are incompletely understood. Here we show that salt-inducible kinase 2 (SIK2) is overexpressed in adipocyte-rich metastatic deposits compared with ovarian primary lesions. Overexpression of SIK2 in ovarian cancer cells promotes abdominal metastasis while SIK2 depletion prevents metastasis in vivo. Importantly, adipocytes induce calcium-dependent activation and autophosphorylation of SIK2. Activated SIK2 plays a dual role in augmenting AMPK-induced phosphorylation of acetyl-CoA carboxylase and in activating the PI3K/AKT pathway through p85α-S154 phosphorylation. These findings identify SIK2 at the apex of the adipocyte-induced signaling cascades in cancer cells and make a compelling case for targeting SIK2 for therapy in ovarian cancer. PMID:27478041

  10. Gastric-type Endocervical Adenocarcinoma: An Aggressive Tumor With Unusual Metastatic Patterns and Poor Prognosis.

    PubMed

    Karamurzin, Yevgeniy S; Kiyokawa, Takako; Parkash, Vinita; Jotwani, Anjali R; Patel, Prusha; Pike, Malcolm C; Soslow, Robert A; Park, Kay J

    2015-11-01

    Gastric-type adenocarcinoma of the uterine cervix (GAS) is a rare variant of mucinous endocervical adenocarcinoma not etiologically associated with human papillomavirus (HPV) infection, with minimal deviation adenocarcinoma (MDA) at the well-differentiated end of the morphologic spectrum. These tumors are reported to have worse prognosis than usual HPV associated endocervical adenocarcinoma (UEA). A retrospective review of GAS was performed from the pathology databases of 3 institutions spanning 20 years. Stage, metastatic patterns, and overall survival were documented. Forty GAS cases were identified, with clinical follow-up data available for 38. The tumors were subclassified as MDA (n=13) and non-MDA GAS (n=27). Two patients were syndromic (1 Li-Fraumeni, 1 Peutz-Jeghers). At presentation, 59% were advanced stage (FIGO II to IV), 50% had lymph node metastases, 35% had ovarian involvement, 20% had abdominal disease, 39% had at least 1 site of metastasis at the time of initial surgery, and 12% of patients experienced distant recurrence. The metastatic sites included lymph nodes, adnexa, omentum, bowel, peritoneum, diaphragm, abdominal wall, bladder, vagina, appendix, and brain. Follow-up ranged from 1.4 to 136.0 months (mean, 33.9 mo); 20/38 (52.6%) had no evidence of disease, 3/38 (7.9%) were alive with disease, and 15/38 (39.5%) died of disease. Disease-specific survival at 5 years was 42% for GAS versus 91% for UEA. There were no survival differences between MDA and non-MDA GAS. GAS represents a distinct, biologically aggressive type of endocervical adenocarcinoma. The majority of patients present at advanced stage and pelvic, abdominal, and distant metastases are not uncommon. PMID:26457350

  11. Immune cells in primary and metastatic gastrointestinal stromal tumors (GIST)

    PubMed Central

    Cameron, Silke; Gieselmann, Marieke; Blaschke, Martina; Ramadori, Giuliano; Füzesi, Laszlo

    2014-01-01

    We have previously described immune cells in untreated primary gastrointestinal stromal tumors (GIST). Here we compare immune cells in metastatic and primary GIST, and describe their chemoattractants. For this purpose, tissue microarrays from 196 patients, 188 primary and 51 metastasized GIST were constructed for paraffin staining. Quantitative analysis was performed for cells of macrophage lineage (Ki-M1P, CD68), T-cells (CD3, CD56) and B-cells (CD20). Chemokine gene-expression was evaluated by real-time RT-PCR. Immuno-localisation was verified by immunofluorescence. Ki-M1P+ cells were the predominant immune cells in both primary and metastatic GIST (2 8.8% ± 7.1, vs. 26.7% ± 6.3). CD68+ macrophages were significantly fewer, with no significant difference between primary GIST (3.6% ± 2.1) and metastases (4.6% ± 1.5). CD3+ T-cells were the most dominant lymphocytes with a significant increase in metastases (7.3% ± 2.3 vs. 2.2% ± 1.8 in primary GIST, P < 0.01). The percentage of CD56+ NK-cells was 1.1% ± 0.9 in the primary, and 2.4 ± 0.7 (P < 0.05) in the metastases. The number of CD20+ B-cells was generally low with 0.6% ± 0.7 in the primary and 1.8% ± 0.3 (P < 0.05) in the metastases. Analysis of the metastases showed significantly more Ki-M1P+ cells in peritoneal metastases (31.8% ± 7.4 vs. 18.2% ± 3.7, P < 0.01), whilst CD3+ T-cells were more common in liver metastases (11.7% ± 1.8 vs. 4.4% ± 2.6, P < 0.01). The highest transcript expression was seen for monocyte chemotactic protein 1 (MCP1/CCL2), macrophage inflammatory protein 1α (MIP-1α/CCL3) and the pro-angiogenic growth-related oncoprotein 1 (Gro-α/CXCL-1). Whilst the ligands were predominantly expressed in tumor cells, their receptors were mostly present in immune cells. This locally specific microenvironment might influence neoplastic progression of GIST at the different metastatic sites. PMID:25120735

  12. Biological Therapy in Treating Patients With Metastatic Cancer

    ClinicalTrials.gov

    2013-02-21

    Breast Cancer; Colorectal Cancer; Extrahepatic Bile Duct Cancer; Gallbladder Cancer; Gastric Cancer; Head and Neck Cancer; Liver Cancer; Lung Cancer; Metastatic Cancer; Ovarian Cancer; Pancreatic Cancer; Testicular Germ Cell Tumor

  13. CD151-α3β1 integrin complexes suppress ovarian tumor growth by repressing slug-mediated EMT and canonical Wnt signaling.

    PubMed

    Baldwin, Lauren A; Hoff, John T; Lefringhouse, Jason; Zhang, Michael; Jia, Changhe; Liu, Zeyi; Erfani, Sonia; Jin, Hongyan; Xu, Mei; She, Qing-Bai; van Nagell, John R; Wang, Chi; Chen, Li; Plattner, Rina; Kaetzel, David M; Luo, Jia; Lu, Michael; West, Dava; Liu, Chunming; Ueland, Fred R; Drapkin, Ronny; Zhou, Binhua P; Yang, Xiuwei H

    2014-12-15

    Human ovarian cancer is diagnosed in the late, metastatic stages but the underlying mechanisms remain poorly understood. We report a surprising functional link between CD151-α3β1 integrin complexes and the malignancy of serous-type ovarian cancer. Analyses of clinical specimens indicate that CD151 expression is significantly reduced or diminished in 90% of metastatic lesions, while it remains detectable in 58% of primary tumors. These observations suggest a putative tumor-suppressing role of CD151 in ovarian cancer. Indeed, our analyses show that knocking down CD151 or α3 integrin enhances tumor cell proliferation, growth and ascites production in nude mice. These changes are accompanied by impaired cell-cell contacts and aberrant expression of E-cadherin, Mucin 5AC and fibronectin, largely reminiscent of an epithelial to mesenchymal transition (EMT)-like change. Importantly, Slug, a master regulator of EMT, is markedly elevated. Knocking down Slug partially restores CD151-α3β1 integrin complex-dependent suppression of cell proliferation. Moreover, disruption of these adhesion protein complexes is accompanied by a concomitant activation of canonical Wnt signaling, including elevated levels of β-catenin and Axin-2 as well as resistance to the inhibition in β-catenin-dependent transcriptional complexes. Together, our study demonstrates that CD151-α3β1 integrin complexes regulate ovarian tumor growth by repressing Slug-mediated EMT and Wnt signaling. PMID:25356755

  14. CD151-α3β1 integrin complexes suppress ovarian tumor growth by repressing slug-mediated EMT and canonical Wnt signaling

    PubMed Central

    Zhang, Michael; Jia, Changhe; Liu, Zeyi; Erfani, Sonia; Jin, Hongyan; Xu, Mei; She, Qing-Bai; van Nagell, John R.; Wang, Chi; Chen, Li; Plattner, Rina; Kaetzel, David M.; Luo, Jia; Lu, Michael; West, Dava; Liu, Chunming; Ueland, Fred R.; Drapkin, Ronny; Zhou, Binhua P.; Yang, Xiuwei H.

    2014-01-01

    Human ovarian cancer is diagnosed in the late, metastatic stages but the underlying mechanisms remain poorly understood. We report a surprising functional link between CD151-α3β1 integrin complexes and the malignancy of serous-type ovarian cancer. Analyses of clinical specimens indicate that CD151 expression is significantly reduced or diminished in 90% of metastatic lesions, while it remains detectable in 58% of primary tumors. These observations suggest a putative tumor-suppressing role of CD151 in ovarian cancer. Indeed, our analyses show that knocking down CD151 or α3 integrin enhances tumor cell proliferation, growth and ascites production in nude mice. These changes are accompanied by impaired cell-cell contacts and aberrant expression of E-cadherin, Mucin 5AC and fibronectin, largely reminiscent of an epithelial to mesenchymal transition (EMT)-like change. Importantly, Slug, a master regulator of EMT, is markedly elevated. Knocking down Slug partially restores CD151-α3β1 integrin complex-dependent suppression of cell proliferation. Moreover, disruption of these adhesion protein complexes is accompanied by a concomitant activation of canonical Wnt signaling, including elevated levels of β-catenin and Axin-2 as well as resistance to the inhibition in β-catenin-dependent transcriptional complexes. Together, our study demonstrates that CD151-α3β1 integrin complexes regulate ovarian tumor growth by repressing Slug-mediated EMT and Wnt signaling. PMID:25356755

  15. Tumor-to-tumor metastasis: an unusual case of breast cancer metastatic to a solitary fibrous tumor

    PubMed Central

    Velez-Cubian, Frank O.; Gabordi, Robert C.; Smith, Prudence V.

    2016-01-01

    Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm that most commonly involves the visceral or parietal pleura, but that has also been described arising from virtually all organs. This neoplasm exhibits rich vascularity, a characteristic it shares with renal cell carcinoma, making these tumors especially suitable for harboring metastases. We present a case of a 64-year-old woman with history of right breast cancer treated six years previously and who presents with a left pulmonary SFT containing metastatic invasive ductal breast carcinoma as well as a synchronous contralateral primary adenocarcinoma of the lung. The literature on tumor-to-tumor metastasis is then reviewed. PMID:27293861

  16. Tumor-to-tumor metastasis: an unusual case of breast cancer metastatic to a solitary fibrous tumor.

    PubMed

    Velez-Cubian, Frank O; Gabordi, Robert C; Smith, Prudence V; Toloza, Eric M

    2016-06-01

    Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm that most commonly involves the visceral or parietal pleura, but that has also been described arising from virtually all organs. This neoplasm exhibits rich vascularity, a characteristic it shares with renal cell carcinoma, making these tumors especially suitable for harboring metastases. We present a case of a 64-year-old woman with history of right breast cancer treated six years previously and who presents with a left pulmonary SFT containing metastatic invasive ductal breast carcinoma as well as a synchronous contralateral primary adenocarcinoma of the lung. The literature on tumor-to-tumor metastasis is then reviewed. PMID:27293861

  17. [Preserving ovarian function in the treatment of epithelial and special (other) malignant ovarian tumors].

    PubMed

    Kolstad, P

    1987-10-01

    About 90% of malignant tumors of the ovary in Scandinavia develop from the germinal epithelium. There are great differences in the incidence rates between countries in the Western world and in Africa and Asia. The WHO classification of ovarian malignancies is generally used. The epithelial tumors comprise the serous, mucinous, endometrioid, clear cell, undifferentiated and mixed true carcinomas. In addition, borderline lesions of especially the serous and mucinous types are of interest when the question of preservation of ovarian function comes into notice. Conservative surgery, which means removal of only the afflicted ovary should be restricted to young women of the childbearing age who want to preserve the possibility of becoming pregnant. However, certain prerequisites must be fulfilled. The tumor must be located to one ovary only (Stage Ia) and must be either a borderline lesion or a Grade 1 true carcinoma of either the serous, mucinous or endometrioid type. There must be no ascites and peritoneal washings must be negative for cancer cells. Germ cell tumors are usually found in young women. Only the dysgerminomas are regularly bilateral in 10-15% of the cases. All other germ cell tumors are rarely bilateral. But both in borderline lesions, Grade 1 true carcinomas, and in germ cell tumors, a biopsy of the normal looking contralateral ovary should always be performed. Endodermal sinus tumors and immature teratomas may well be treated conservatively by surgery, but modern triple chemotherapy (VAC, PVB) must be added. Granulosa theca cell tumors are bilateral in only about 5% of the cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2824278

  18. A new tumor marker: CA125 for ovarian carcinomas

    SciTech Connect

    Sakahara, H.; Endo, K.; Nakajima, K.; Nakashima, T.; Koizumi, M.; Ohta, H.; Torizuka, K.; Konishi, I.; Fujii, S.; Mori, T.

    1985-05-01

    To evaluate CA125 as a tumor marker for ovarian carcinomas, CA125 concentrations were measured by the simultaneous immunoradiometric assay. The binding of I-125 labeled monoclonal antibody to the bead-bound antigen was greatly influenced by many factors, such as the incubation time, pH, IgG concentrations of samples, the sequence of addition of the tracer and samples and so on. By applying the forward two-step assay, diminished binding was observed than in the simultaneous assay, probably due to the relatively low affinity of the antibody. This simultaneous immunoradiometric assay resulted in the ''prozone'' or ''hook'' effect at high CA125 samples and proper dilution was necessary to determine the accurate CA125 values. All 72 normal control subjects had low concentrations of under 35 U/ml. Elevated serum CA125 was observed in 43% (9/21) cases with malignant ovarian tumors, depending on the stage and the histopathological findings. All 4 serous cystadenocarcinomas and 2 of 3 endometrioid carcinomas were positive and the measurement of serum CA125 was useful in the sequential monitoring of these cases. In contrast, 51 benign gynecological diseases, none had elevated serum CA125 except one with follicular cyst. Among 75 cases with non-gynecological benign and malignant diseases, only 1 of 12 gastric carcinomas and 2 of 13 pancreatic carcinomas had elevated CA125 levels. In summary, CA125 is a promising and relatively specific marker for ovarian carcinomas.

  19. The HMG-CoA reductase inhibitor, simvastatin, exhibits anti-metastatic and anti-tumorigenic effects in ovarian cancer

    PubMed Central

    Sheng, Xiugui; Han, Xiaoyun; Schointuch, Monica N.; Gilliam, Timothy P.; Gehrig, Paola A.; Zhou, Chunxiao; Bae-Jump, Victoria L.

    2016-01-01

    Ovarian cancer is the 5th leading cause of cancer death among women in the United States. The mevalonate pathway is thought to be a potential oncogenic pathway in the pathogenesis of ovarian cancer. Simvastatin, a 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR) inhibitor, is a widely used drug for inhibiting the synthesis of cholesterol and may also have anti-tumorigenic activity. Our goal was to evaluate the effects of simvastatin on ovarian cancer cell lines, primary cultures of ovarian cancer cells and in an orthotopic ovarian cancer mouse model. Simvastatin significantly inhibited cellular proliferation, induced cell cycle G1 arrest and apoptosis, and caused cellular stress via reduction in the enzymatic activity of HMGCR and inhibition of the MAPK and mTOR pathways in ovarian cancer cells. Furthermore, simvastatin induced DNA damage and reduced cell adhesion and invasion. Simvastatin also exerted anti-proliferative effects on primary cell cultures of ovarian cancer. Treatment with simvastatin in an orthotopic mouse model reduced ovarian tumor growth, coincident with decreased Ki-67, HMGCR, phosphorylated-Akt and phosphorylated-p42/44 protein expression. Our findings demonstrate that simvastatin may have therapeutic benefit for ovarian cancer treatment and be worthy of further exploration in clinical trials. PMID:26503475

  20. New ways to successfully target tumor vasculature in ovarian cancer

    PubMed Central

    Yang, Xiaoyun; Shen, Fangrong; Hu, Wei; Coleman, Robert L.; Sood, Anil K.

    2015-01-01

    Purpose of review The aim of this paper was to review the recent literature on potential therapeutic strategies for overcoming resistance to anti-VEGF drugs in ovarian cancer. Recent findings Although clinical benefits of anti-VEGF therapy were observed in ovarian cancer treatment trials, this use yielded only modest improvement in progression-free survival, and with the exception of cediranib no effect on overall survival. Adaptive resistance and escape from anti-angiogenesis therapy is likely a multifactorial process, including induction of hypoxia, vascular modulators and the immune response. New drugs targeting the tumor vasculature or other components of the surrounding microenvironment have shown promising results. Summary When to start and end antiangiogenesis therapy and the choice of optimal treatment combinations remain controversial. Further evaluation of personalized novel angiogenesis-based therapy is warranted. Defining the critical interaction of these agents and pathways and the appropriate predictive markers will become an increasingly important objective for effective treatment. PMID:25502429

  1. Well-Differentiated Grade 2, Type 3 Gastrointestinal Neuroendocrine Tumour with Bilateral Metastatic Ovarian Involvement: Report of an Unusual Case

    PubMed Central

    Manneh, Ray; Castellano, Daniel; Caso, Oscar; Loinaz, Carmelo; Jiménez, Jesús; Estenoz, Juana; Calatayud, Maria; Sepúlveda, Juan M.; García-Carbonero, Rocio

    2016-01-01

    Treatment of metastatic gastric neuroendocrine tumours (NETs) is challenging. In oligometastatic cases, surgical resection is recommended whenever possible. Somatostatin analogues have been used to decrease gastrin levels, and available evidence suggests that these drugs can also reduce recurrences. Here we present a highly unusual case involving a patient with a well-differentiated grade 2, type 3 gastric NET with exclusive metastatic bilateral ovarian involvement. To our knowledge, this is the first such case reported in the literature, as the cause of ovarian involvement is usually due to local invasion rather than metastasis. We believe this case is of interest not only due to the unusual presentation, but also because it makes us consider adjuvant treatment with somatostatin analogues in patients with low-grade tumours and a positive postoperative octreoscan. PMID:27239181

  2. IL-12 secreting tumor-targeted chimeric antigen receptor T cells eradicate ovarian tumors in vivo

    PubMed Central

    Koneru, Mythili; Purdon, Terence J.; Spriggs, David; Koneru, Susmith; Brentjens, Renier J.

    2015-01-01

    A novel approach for the treatment of ovarian cancer includes immunotherapy with genetically engineered T cells targeted to ovarian cancer cell antigens. Using retroviral transduction, T cells can be created that express an artificial T cell receptor (TCR) termed a chimeric antigen receptor (CAR). We have generated a CAR, 4H11-28z, specific to MUC-16ecto antigen, which is the over-expressed on a majority of ovarian tumor cells and is the retained portion of MUC-16 after cleavage of CA-125. We previously demonstrated that T cells modified to express the 4H11-28z CAR eradicate orthotopic human ovarian cancer xenografts in SCID-Beige mice. However, despite the ability of CAR T cells to localize to tumors, their activation in the clinical setting can be inhibited by the tumor microenvironment, as is commonly seen for endogenous antitumor immune response. To potentially overcome this limitation, we have recently developed a construct that co-expresses both MUC16ecto CAR and IL-12 (4H11-28z/IL-12). In vitro, 4H11-28z/IL-12 CAR T cells show enhanced proliferation and robust IFNγ secretion compared to 4H11-28z CAR T cells. In SCID-Beige mice with human ovarian cancer xenografts, IL-12 secreting CAR T cells exhibit enhanced antitumor efficacy as determined by increased survival, prolonged persistence of T cells, and higher systemic IFNγ. Furthermore, in anticipation of translating these results into a phase I clinical trial which will be the first to study IL-12 secreting CAR T cells in ovarian cancer, an elimination gene has been included to allow for deletion of CAR T cells in the context of unforeseen or off-tumor on-target toxicity. PMID:25949921

  3. Anti-tumor immunity generated by photodynamic therapy in a metastatic murine tumor model

    NASA Astrophysics Data System (ADS)

    Castano, Ana P.; Hamblin, Michael R.

    2005-04-01

    Photodynamic therapy (PDT) is a modality for the treatment of cancer involving excitation of photosensitizers with harmless visible light producing reactive oxygen species. The major biological effects of PDT are apoptosis of tumor cells, destruction of the blood supply and activation of the immune system. The objective of this study is to compare in an animal model of metastatic cancer, PDT alone and PDT combined with low-dose cyclophosphamide (CY). Since the tumor we used is highly metastatic, it is necessary to generate anti-tumor immunity using PDT to both cure the primary tumor and prevent death from metastasis. This immunity may be potentiated by low dose CY. In our model we used J774 cells (a Balb/c reticulum cell sarcoma line with the characteristics of macrophages) and the following PDT regimen: benzoporphyrin derivative monoacid ring A (BPD, 2mg/kg injected IV followed after 15 min by 150 J/cm2 of 690-nm light). CY (50 mg/kg i.p.) was injected 48 hours before light delivery. BPD-PDT led to complete regression of the primary tumor in more than half the mice but no permanent cures were obtained. BPD-PDT in combination with CY led to 60% permanent cures. CY alone gave no permanent cures but did provide a survival advantage. To probe permanent immunity cured animals were rechallenged with the same tumor cell line and the tumors were rejected in 71% of mice cured with BPD-PDT plus CY. We conclude that BPD-PDT in combination with CY gives best overall results and that this is attributable to immunological response activation in addition to PDT-mediated destruction of the tumor.

  4. Sequence and structure of the Drosophila melanogaster ovarian tumor gene and generation of an antibody specific for the ovarian tumor protein.

    PubMed Central

    Steinhauer, W R; Walsh, R C; Kalfayan, L J

    1989-01-01

    Sequencing cDNA and genomic DNA from the ovarian tumor gene revealed a gene with seven introns spanning 4.5 kilobases. The proline-rich, hydrophilic otu protein is novel. An antibody prepared to a beta-gal-otu fusion protein recognized a 110-kilodalton ovarian protein which was altered in the ovaries of otu gene mutants. Images PMID:2511440

  5. Uterine tumors resembling ovarian sex cord tumors: A case report and literature review

    PubMed Central

    CETINKAYA, NILUFER; BAS, SEVDA; CUYLAN, ZELIHA FIRAT; ERDEM, OZLEM; ERKAYA, SALIM; GUNGOR, TAYFUN

    2016-01-01

    Uterine tumors with ovarian sex cord-like elements are a rarely observed type of uterine body tumor with unknown etiology, and are divided into two groups: Endometrial stromal tumors with sex cord-like elements (ESTSCLEs) and uterine tumors resembling ovarian sex cord tumors (UTROSCTs). While ESTSCLEs are commonly associated with metastasis and recurrence, there is limited data in the relevant literature concerning the behavior of UTROSCTs. However, UTROSCTs are typically benign in nature. Although case numbers are limited, extra-uterine or lymph node metastasis has been reported. Surgical approaches may be altered according to the patient's age and desire for future fertility. Hysterectomies with bilateral salpingo-oopherectomy or hysteroscopic tumor resection are reported to be safe surgical treatment options. However, in the current report, a case of UTROSCT initially misdiagnosed as adenosarcoma following hysteroscopic tumor resection is presented. Staging surgery revealed the precise diagnosis of the tumor using appropriate immunohistochemical evaluations, and led to the discovery of a secondary tumor focus in the myometrium, adjacent to the location of the previously excised tumor. Thus, hysteroscopic resection is questionable as a definitive surgical treatment in patients exhibiting UTROSCT. If hysteroscopic resection is the selected treatment, close follow-up with diagnostic imaging is recommended. PMID:26893767

  6. Is the Blood-Brain Barrier Relevant in Metastatic Germ Cell Tumor?

    SciTech Connect

    Azar, Jose M. Schneider, Bryan P.; Einhorn, Lawrence H.

    2007-09-01

    Purpose: Germ cell tumors are uniquely chemosensitive and curable, even with advanced metastatic disease. Central nervous system recurrence can terminate a complete remission in other chemosensitive tumors, such as small cell lung cancer, because of the blood-brain barrier (BBB). We propose to document that the BBB is also relevant in germ cell tumors despite their dramatic chemosensitivity. Methods and Materials: We present five cases illustrating the concept of the BBB in patients with metastatic testicular cancer treated with chemotherapy. Results: In our large series of patients with metastatic testicular cancer treated with chemotherapy, we identified 5 unique patients. These patients were rendered free of disease only to experience relapse in the brain alone. This included 1 patient who initially had good-risk metastatic disease by means of the International Germ Cell Collaborative Group staging system at the onset of chemotherapy. Conclusions: The BBB is relevant in patients with metastatic testicular cancer.

  7. Ovarian tumor-initiating cells display a flexible metabolism

    SciTech Connect

    Anderson, Angela S.; Roberts, Paul C.; Frisard, Madlyn I.; Hulver, Matthew W.; Schmelz, Eva M.

    2014-10-15

    An altered metabolism during ovarian cancer progression allows for increased macromolecular synthesis and unrestrained growth. However, the metabolic phenotype of cancer stem or tumor-initiating cells, small tumor cell populations that are able to recapitulate the original tumor, has not been well characterized. In the present study, we compared the metabolic phenotype of the stem cell enriched cell variant, MOSE-L{sub FFLv} (TIC), derived from mouse ovarian surface epithelial (MOSE) cells, to their parental (MOSE-L) and benign precursor (MOSE-E) cells. TICs exhibit a decrease in glucose and fatty acid oxidation with a concomitant increase in lactate secretion. In contrast to MOSE-L cells, TICs can increase their rate of glycolysis to overcome the inhibition of ATP synthase by oligomycin and can increase their oxygen consumption rate to maintain proton motive force when uncoupled, similar to the benign MOSE-E cells. TICs have an increased survival rate under limiting conditions as well as an increased survival rate when treated with AICAR, but exhibit a higher sensitivity to metformin than MOSE-E and MOSE-L cells. Together, our data show that TICs have a distinct metabolic profile that may render them flexible to adapt to the specific conditions of their microenvironment. By better understanding their metabolic phenotype and external environmental conditions that support their survival, treatment interventions can be designed to extend current therapy regimens to eradicate TICs. - Highlights: • Ovarian cancer TICs exhibit a decreased glucose and fatty acid oxidation. • TICs are more glycolytic and have highly active mitochondria. • TICs are more resistant to AICAR but not metformin. • A flexible metabolism allows TICs to adapt to their microenvironment. • This flexibility requires development of specific drugs targeting TIC-specific changes to prevent recurrent TIC outgrowth.

  8. Mucinous Borderline Ovarian Tumor in Very Old Aged Postmenopausal Woman

    PubMed Central

    Lee, Seung-Hee; Lee, Hae-Hyeog; Lee, Arum; Kim, Yeon-Suk; Jeon, Dong-Su; Kwak, Jeong Ja; Yang, Yo-Sep

    2015-01-01

    Mucinous borderline ovarian tumors (BOTs) occur most often in women between the ages of 20 and 30. Early-stage detection of the condition has a more favorable prognosis. In this case report, the authors present an elderly 93-year old woman who visited our hospital due to severe abdominal pain after being diagnosed with a pelvic mass 2 years ago and not undergoing any treatment since the diagnosis was made. She underwent emergency left salpingo-oophorectomy and was diagnosed with mucinous BOT according to biopsy results. PMID:26793682

  9. Metastatic ovarian papillary cystadenocarcinoma to the small intestine serous surface: report of a case of high-grade histopathologic malignancy

    PubMed Central

    2014-01-01

    Ovarian cystadenocarcinoma is characterized by marked heterogeneity and may be composed of an admixture of histologic growth patterns, including acinar, papillary and solid. In the present study, a case of isolated small intestine metastasis of ovarian papillary cystadenocarcinoma was reported. A 7-year-old female mixed-breed dog presented with a mass in the left upper quadrant with progressive enlargement of the abdomen, periodic bloody discharge from the vulva and incontinence. The tumor was histologically characterized by the presence of cysts and proliferation of papillae, both lined by single- or multi-layered pleomorphic epithelial cells. Furthermore, the mass was composed by intense cellular and nuclear pleomorphism and numerous mitotic figures. These findings indicate a tumor of high-grade malignancy with infiterative tumor cells resembling the papillary ovarian tumor in the serosal surface of the small intestine along with an intact serosa. Immunohistochemically, tumor was positive for CK7 and negative immunoreactivity for CK20. The histopathologic features coupled with the CK7 immunoreactivity led to a diagnosis of high grade ovarian papillary cystadenocarcinoma. To the best of our knowledge, this is the first case of small intestine serousal surface metastasis from ovarian papillary cystadenocarcinoma. PMID:24636424

  10. Etiology of Ascites and Pleural Effusion Associated with Ovarian Tumors: Literature Review and Case Reports of Three Ovarian Tumors Presenting with Massive Ascites, but without Peritoneal Dissemination

    PubMed Central

    Miyoshi, Ai; Miyatake, Takashi; Hara, Takeya; Tanaka, Asuka; Komura, Naoko; Komiya, Shinnosuke; Kanao, Serika; Takeda, Masumi; Mimura, Mayuko; Nagamatsu, Masaaki; Yokoi, Takeshi

    2015-01-01

    Borderline ovarian tumors are benign but relatively large tumors that are often initially mistaken as ovarian cancers. We report three cases of stage I borderline ovarian tumors having massive ascites that we (preoperatively) suspected of being advanced ovarian cancer. The three patients (35, 47, and 73 years old) reported feeling fullness of the abdomen before consulting their gynecologist. By CT scan, they were diagnosed with a pelvic tumor accompanied by massive ascites, the diameters of which were 11, 20, and 11 cm, respectively. Postsurgical pathology showed all were stage I borderline ovarian tumors without dissemination; two were mucinous and one was serous. The amount of ascites was 6,300, 2,600, and 3,600 mL, respectively, and was serous in all. Cytodiagnosis of the ascites found that one was positive for tumor cells and two were negative. After resection of the mass, the ascites disappeared in all three cases. No pleural effusion was present at any time. The literature is reviewed concerning ascites and pleural effusions linked to ovarian tumors, and a supposition is forwarded of why pleural effusion presents sporadically in these cases. PMID:26858849

  11. Circulating tumor DNA and circulating tumor cells in metastatic triple negative breast cancer patients.

    PubMed

    Madic, Jordan; Kiialainen, Anna; Bidard, Francois-Clement; Birzele, Fabian; Ramey, Guillemette; Leroy, Quentin; Rio Frio, Thomas; Vaucher, Isabelle; Raynal, Virginie; Bernard, Virginie; Lermine, Alban; Clausen, Inga; Giroud, Nicolas; Schmucki, Roland; Milder, Maud; Horn, Carsten; Spleiss, Olivia; Lantz, Olivier; Stern, Marc-Henri; Pierga, Jean-Yves; Weisser, Martin; Lebofsky, Ronald

    2015-05-01

    Circulating tumor DNA (ctDNA) is a new circulating tumor biomarker which might be used as a prognostic biomarker in a way similar to circulating tumor cells (CTCs). Here, we used the high prevalence of TP53 mutations in triple negative breast cancer (TNBC) to compare ctDNA and CTC detection rates and prognostic value in metastatic TNBC patients. Forty patients were enrolled before starting a new line of treatment. TP53 mutations were characterized in archived tumor tissues and in plasma DNA using two next generation sequencing (NGS) platforms in parallel. Archived tumor tissue was sequenced successfully for 31/40 patients. TP53 mutations were found in 26/31 (84%) of tumor samples. The same mutation was detected in the matched plasma of 21/26 (81%) patients with an additional mutation found only in the plasma for one patient. Mutated allele fractions ranged from 2 to 70% (median 5%). The observed correlation between the two NGS approaches (R(2) = 0.903) suggested that ctDNA levels data were quantitative. Among the 27 patients with TP53 mutations, CTC count was ≥1 in 19 patients (70%) and ≥5 in 14 patients (52%). ctDNA levels had no prognostic impact on time to progression (TTP) or overall survival (OS), whereas CTC numbers were correlated with OS (p = 0.04) and marginally with TTP (p = 0.06). Performance status and elevated LDH also had significant prognostic impact. Here, absence of prognostic impact of baseline ctDNA level suggests that mechanisms of ctDNA release in metastatic TNBC may involve, beyond tumor burden, biological features that do not dramatically affect patient outcome. PMID:25307450

  12. Changes in expression of differentiation markers between normal ovarian cells and derived tumors.

    PubMed Central

    Van Niekerk, C. C.; Ramaekers, F. C.; Hanselaar, A. G.; Aldeweireldt, J.; Poels, L. G.

    1993-01-01

    The marker profile of 18 samples of normal human ovarian tissues and 138 samples of their derived tumors was established using 51 monoclonal antibodies directed against intermediate filaments, ovarian carcinoma-specific antigens, general tumor-associated antigens and MHC-I/II antigens. Our data show that vimentin and keratins 7, 8, 18, and 19 were found in both epithelial and some nonepithelial ovarian tumors. Several tumor samples contained additional keratins 4, 10, 13, and 14, as well as desmin. BW 495/36 and to a lesser extent HMFG-2 were usually found in all ovarian tumors that contained simple epithelial keratins, except the absence of HMFG-2 in gonadal tumors as well as in dysgerminomas. In contrast to the keratin antibodies, these two panepithelial antibodies were negative in normal mesothelial cells and granulosa cells of the ovarian follicles. In general, the marker TAG-72 appeared useful for its discrimination between positively stained mucinous adenomas, the ovarian carcinomas as well as germ cell tumors, and the negatively stained gonadal tumors, serous adenomas, and cystomas. OV632 appeared useful in the distinction between negatively stained serous adenomas and positively stained serous carcinomas. In contrast, the monoclonal antibodies OC 125, OV-TL 3, OV-TL 16, and MOv 18 can be considered as pan-ovarian carcinoma markers, however without the discriminative capability as seen for OV632. These ovarian carcinoma-associated antigens were hardly found expressed in gonadal and germ cell tumors, except in the group of endodermal sinus tumors. HLA-I was found to be expressed in almost all nucleated cells, although loss of HLA-I expression was seen in areas of tumor cells. HLA-DR was negative in normal ovarian tissue, but heterogeneous expression was noticed in most of the epithelial tumors. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:7678716

  13. [Hormonal therapy of advanced or relapsed ovarian granulosa cell tumor].

    PubMed

    Sun, H; Bai, P

    2016-07-01

    Ovarian granulosa cell tumor is a rare gynecologic malignancy with hormonal activity. Surgical excision is the standard treatment for this disease. Most patients present excellent short term prognosis, however, late relapse often occurs, even after many years. Viable treatments of advanced or relapsed granulosa cell tumor are still limited, and the optimal therapy method has not been established. Compared with chemotherapy and radiotherapy, hormonal therapy is a well-tolerated treatment which can be administrated over a long period of time without serious side effects, and the combined application of hormones may achieve a better outcome. Therefore, hormonal therapy has been suggested as a potential treatment option for patients with advanced or relapsed granulosa cell tumor, and to extend the tumor-free interval and attenuate the disease progression. Future researches should be focused on the identification of the hormonal therapy which may provide the greatest clinical benefit, comparing and analyzing the effects of different combined therapeutic regimens of hormone drugs, and on the synthesis of drugs highly activating estrogen receptor β expressed in the granulosa cell tumor cells. PMID:27531259

  14. Comprehensive Quantitative Analysis of Ovarian and Breast Cancer Tumor Peptidomes

    SciTech Connect

    Xu, Zhe; Wu, Chaochao; Xie, Fang; Slysz, Gordon W.; Tolic, Nikola; Monroe, Matthew E.; Petyuk, Vladislav A.; Payne, Samuel H.; Fujimoto, Grant M.; Moore, Ronald J.; Fillmore, Thomas L.; Schepmoes, Athena A.; Levine, Douglas; Townsend, Reid; Davies, Sherri; Li, Shunqiang; Ellis, Matthew; Boja, Emily; Rivers, Robert; Rodriguez, Henry; Rodland, Karin D.; Liu, Tao; Smith, Richard D.

    2015-01-02

    Aberrant degradation of proteins is associated with many pathological states, including cancers. Mass spectrometric analysis of tumor peptidomes, the intracellular and intercellular products of protein degradation, has the potential to provide biological insights on proteolytic processing in cancer. However, attempts to use the information on these smaller protein degradation products from tumors for biomarker discovery and cancer biology studies have been fairly limited to date, largely due to the lack of effective approaches for robust peptidomics identification and quantification, and the prevalence of confounding factors and biases associated with sample handling and processing. Herein, we have developed an effective and robust analytical platform for comprehensive analyses of tissue peptidomes, which is suitable for high throughput quantitative studies. The reproducibility and coverage of the platform, as well as the suitability of clinical ovarian tumor and patient-derived breast tumor xenograft samples with post-excision delay of up to 60 min before freezing for peptidomics analysis, have been demonstrated. Moreover, our data also show that the peptidomics profiles can effectively separate breast cancer subtypes, reflecting tumor-associated protease activities. Peptidomics complements results obtainable from conventional bottom-up proteomics, and provides insights not readily obtainable from such approaches.

  15. Comprehensive Quantitative Analysis of Ovarian and Breast Cancer Tumor Peptidomes

    SciTech Connect

    Xu, Zhe; Wu, Chaochao; Xie, Fang; Slysz, Gordon W.; Tolic, Nikola; Monroe, Matthew E.; Petyuk, Vladislav A.; Payne, Samuel H.; Fujimoto, Grant M.; Moore, Ronald J.; Fillmore, Thomas L.; Schepmoes, Athena A.; Levine, Douglas; Townsend, Reid; Davies, Sherri; Li, Shunqiang; Ellis, Matthew; Boja, Emily; Rivers, Robert; Rodriguez, Henry; Rodland, Karin D.; Liu, Tao; Smith, Richard D.

    2015-01-01

    Aberrant degradation of proteins is associated with many pathological states, including cancers. Mass spectrometric analysis of tumor peptidomes, the intracellular and intercellular products of protein degradation, has the potential to provide biological insights on proteolytic processing in cancer. However, attempts to use the information on these smaller protein degradation products from tumors for biomarker discovery and cancer biology studies have been fairly limited to date, largely due to the lack of effective approaches for robust peptidomics identification and quantification, and the prevalence of confounding factors and biases associated with sample handling and processing. Herein, we have developed an effective and robust analytical platform for comprehensive analyses of tissue peptidomes, and which is suitable for high throughput quantitative studies. The reproducibility and coverage of the platform, as well as the suitability of clinical ovarian tumor and patient-derived breast tumor xenograft samples with post-excision delay of up to 60 min before freezing for peptidomics analysis, have been demonstrated. Moreover, our data also show that the peptidomics profiles can effectively separate breast cancer subtypes, reflecting tumor-associated protease activities. Peptidomics complements results obtainable from conventional bottom-up proteomics, and provides insights not readily obtainable from such approaches.

  16. Different staining patterns of ovarian Brenner tumor and the associated mucinous tumor.

    PubMed

    Roma, Andres A; Masand, Ramya P

    2015-02-01

    The association of ovarian Brenner tumors and adjacent mucinous tumors is well known but not completely understood. In this study, we analyzed immunohistochemical markers on Brenner tumors and their associated mucinous tumor to explore Mullerian as well as Wolffian and germ cell derivation and determine if the mucinous component is independent or related to the Brenner tumor. Of 32 consecutive cases of Brenner tumors, 8 were identified with significant mucinous component, and 7 additional cases included foci of mucinous epithelium within the Brenner transitional nests. All Brenner tumors were diffusely positive for GATA3 and negative for Paired box gene 8, PAX2, and Sal-like protein 4. Interestingly, the areas of mucinous epithelium as well as mucinous tumors, intermixed and adjacent to the Brenner tumor, were negative for all 4 markers; however, occasional basal-like cells retained expression of GATA3. The immunoprofile of mucinous tumors associated with Brenner tumors shares the lack of Mullerian markers PAX2 and Paired box gene 8 with the Brenner tumor but differs in the expression of GATA3 only in the Brenner tumor component. PMID:25596159

  17. Obesity increases tumor aggressiveness in a genetically engineered mouse model of serous ovarian cancer☆

    PubMed Central

    Makowski, Liza; Zhou, Chunxiao; Zhong, Yan; Kuan, Pei Fen; Fan, Cheng; Sampey, Brante P.; Difurio, Megan; Bae-Jump, Victoria L.

    2014-01-01

    Objectives Obesity is associated with increased risk and worse outcomes for ovarian cancer. Thus, we examined the effects of obesity on ovarian cancer progression in a genetically engineered mouse model of serous ovarian cancer. Methods We utilized a unique serous ovarian cancer mouse model that specifically deletes the tumor suppressor genes, Brca1 and p53, and inactivates the retinoblastoma (Rb) proteins in adult ovarian surface epithelial cells, via injection of an adenoviral vector expressing Cre (AdCre) into the ovarian bursa cavity of adult female mice (KpB mouse model). KpB mice were subjected to a 60% calories-derived from fat in a high fat diet (HFD) versus 10% calories from fat in a low fat diet (LFD) to mimic diet-induced obesity. Tumors were isolated at 6 months after AdCre injection and evaluated histologically. Untargeted metabolomic and gene expression profiling was performed to assess differences in the ovarian tumors from obese versus non-obese KpB mice. Results At sacrifice, mice on the HFD (obese) were twice the weight of mice on the LFD (non-obese) (51 g versus 31 g, p = 0.0003). Ovarian tumors were significantly larger in the obese versus non-obese mice (3.7 cm2 versus 1.2 cm2, p = 0.0065). Gene expression and metabolomic profiling indicated statistically significant differences between the ovarian tumors from the obese versus non-obese mice, including metabolically relevant pathways. PMID:24680597

  18. Molecular subtypes of serous borderline ovarian tumor show distinct expression patterns of benign tumor and malignant tumor-associated signatures.

    PubMed

    Curry, Edward W J; Stronach, Euan A; Rama, Nona R; Wang, Yuepeng Y P; Gabra, Hani; El-Bahrawy, Mona A

    2014-03-01

    Borderline ovarian tumors show heterogeneity in clinical behavior. Most have excellent prognosis, although a small percentage show recurrence or progressive disease, usually to low-grade serous carcinoma. The aim of this study was to understand the molecular relationship between these entities and identify potential markers of tumor progression and therapeutic targets. We studied gene expression using Affymetrix HGU133plus2 GeneChip microarrays in 3 low-grade serous carcinomas, 13 serous borderline tumors and 8 serous cystadenomas. An independent data set of 18 serous borderline tumors and 3 low-grade serous carcinomas was used for validation. Unsupervised clustering revealed clear separation of benign and malignant tumors, whereas borderline tumors showed two distinct groups, one clustering with benign and the other with malignant tumors. The segregation into benign- and malignant-like borderline molecular subtypes was reproducible on applying the same analysis to an independent publicly available data set. We identified 50 genes that separate borderline tumors into their subgroups. Functional enrichment analysis of genes that separate borderline tumors to the two subgroups highlights a cell adhesion signature for the malignant-like subset, with Claudins particularly prominent. This is the first report of molecular subtypes of borderline tumors based on gene expression profiling. Our results provide the basis for identification of biomarkers for the malignant potential of borderline ovarian tumor and potential therapeutic targets for low-grade serous carcinoma. PMID:23948749

  19. Harnessing Pandemonium: The Clinical Implications of Tumor Heterogeneity in Ovarian Cancer

    PubMed Central

    Blagden, Sarah P.

    2015-01-01

    Heterogeneity has emerged as a key feature of ovarian cancer between different ovarian cancer subtypes; within single ovarian cancer subtypes; and within individual patient tumors. At the genomic level, with the advent of ultra-deep sequencing technologies alongside RNA-Seq, epigenomics, and proteomics, the complexity surrounding heterogeneity has deepened. Here, we summarize the emerging understanding of heterogeneity in cancer as a whole and the key discoveries in this area relating to ovarian cancer. We explore the therapeutic limitations and possibilities posed by heterogeneity and how these will influence the future of ovarian cancer treatment and research. PMID:26175968

  20. Regulation of Ovarian Cancer Stem Cells or Tumor-Initiating Cells

    PubMed Central

    Kwon, Mi Jeong; Shin, Young Kee

    2013-01-01

    Cancer stem cells or tumor-initiating cells (CSC/TICs), which can undergo self-renewal and differentiation, are thought to play critical roles in tumorigenesis, therapy resistance, tumor recurrence and metastasis. Tumor recurrence and chemoresistance are major causes of poor survival rates of ovarian cancer patients, which may be due in part to the existence of CSC/TICs. Therefore, elucidating the molecular mechanisms responsible for the ovarian CSC/TICs is required to develop a cure for this malignancy. Recent studies have indicated that the properties of CSC/TICs can be regulated by microRNAs, genes and signaling pathways which also function in normal stem cells. Moreover, emerging evidence suggests that the tumor microenvironments surrounding CSC/TICs are crucial for the maintenance of these cells. Similarly, efforts are now being made to unravel the mechanism involved in the regulation of ovarian CSC/TICs, although much work is still needed. This review considers recent advances in identifying the genes and pathways involved in the regulation of ovarian CSC/TICs. Furthermore, current approaches targeting ovarian CSC/TICs are described. Targeting both CSC/TICs and bulk tumor cells is suggested as a more effective approach to eliminating ovarian tumors. Better understanding of the regulation of ovarian CSC/TICs might facilitate the development of improved therapeutic strategies for recurrent ovarian cancer. PMID:23528891

  1. A case of carcinoid tumor of the terminal ileum and simultaneous ovarian dermoid cyst.

    PubMed

    Hamada, Hosam

    2011-04-01

    Carcinoid tumors are slow-growing malignant neoplasms associated with an indolent clinical course. About 60% of such tumors are located within the gastrointestinal tract. Here, we describe the first case, to our knowledge, of a carcinoid tumor of the terminal ileum and a simultaneous ovarian dermoid cyst. A 57-year-old woman was presented with abdominal pain, vomiting, and clinical signs of mechanical bowel obstruction. Radiograph and computed tomography scan of the abdomen showed hydroaeric levels. Laparotomy revealed a mass in the terminal ileum and a right ovarian cystic mass. Right hemicolectomy and right oopherectomy were performed. The histopathological workup showed a carcinoid tumor of the terminal ileum and ovarian dermoid cyst. Small intestinal carcinoid tumor, an uncommon disease, has been reported earlier to coincide with various neoplasms. No association between small intestinal carcinoid tumor and ovarian dermoid cyst has been reported earlier in the English literature. PMID:21389861

  2. Risk factors for deep-vein thrombosis and pulmonary thromboembolism in benign ovarian tumor.

    PubMed

    Shiota, Mitsuru; Kotani, Yasushi; Umemoto, Masahiko; Tobiume, Takako; Tsuritani, Mitsuhiro; Shimaoka, Masao; Hoshiai, Hiroshi

    2011-01-01

    Pulmonary thromboembolism (PE) is a serious postoperative complication. Reported rates of PE following gynecologic surgery are between 0.3% and 0.8%, with deep-vein thrombosis (DVT) as the major cause (via seeding of the lungs). Benign ovarian tumors are treated principally by surgery. Possible risk factors for DVT and PE in patients with benign ovarian tumors include tumor size, patient age, and obesity. To date, however, there has been no report addressing the association of these risk factors in patients with benign ovarian tumors. This study offers a retrospective analysis of the incident of preoperative DVT by age, tumor size, and BMI in patients undergoing surgery for benign ovarian tumors. A total of 843 Japanese patients with a preoperative diagnosis of benign ovarian tumor who underwent tumorectomy or adnexectomy at our institution between July 2003 and December 2010 were enrolled. The incidence of preoperative DVT was monitored and statistically stratified by age (< 50 years and ≥ 50 years), largest tumor diameter (< 10 cm and ≥ 10 cm), and BMI (< 25 and ≥ 25). The result indicates that tumor diameter of ≥ 10 cm is not a risk factor for preoperative DVT in patients with benign ovarian tumor. On the other hand, age ≥ 50 years and BMI > 25 are independent risk factors for preoperative DVT in Japan. The patients with each risk factor should be treated with preoperative, intraoperative, and postoperative precautions against development of PE. PMID:21817850

  3. Total En Bloc Spondylectomy for Primary and Metastatic Spine Tumors.

    PubMed

    Mesfin, Addisu; El Dafrawy, Mostafa H; Jain, Amit; Hassanzadeh, Hamid; Kebaish, Khaled M

    2015-11-01

    This study reports the surgical and clinical outcomes of spinal tumors managed with total en bloc spondylectomy. The authors searched their prospectively maintained database for patients undergoing total en bloc spondylectomy between 2001 and 2013. Ten patients (9 men, 1 woman; average age, 50.7 years; range, 42-68 years) were identified. The authors obtained demographic information, surgical outcomes (estimated blood loss, complications), and clinical outcomes (recurrence, survival). All patients had pain and were classified as American Spinal Injury Association grade E. The lesions were located in the thoracic (8 patients) and lumbar (2 patients) spine. Anterior column reconstruction was performed with strut allograft (7 patients), mesh cage (2 patients), and polymethyl methacrylate (1 patient). An average of 2.3 (range, 2-4) of 6 portions of the vertebrae were involved, according to the Kostuik classification. Mean estimated blood loss, operative time, and hospital stay were 3.5 L, 500 minutes, and 7.8 days, respectively. Perioperative complications included pleural tear (2 patients) and aortic tear, vena cava tear, retained sponge, pulmonary embolism, urinary tract infection, pneumothorax, anterior column support failure, and prominent instrumentation requiring removal (1 patient each). Postoperatively, all patients remained classified as American Spinal Injury Association grade E. Two patients had recurrence at distant spinal segments, and 1 had a new lesion in the thigh. Five patients had died (mean, 34.5 months after surgery), and 5 were alive a mean of 19.6 months after surgery (range, 6-48 months). Total en bloc spondylectomy is challenging, but in appropriately selected patients, it can be used to treat primary and metastatic spinal lesions. PMID:26558680

  4. Control of metastatic mammary tumors by laser immunotherapy through local treatment

    NASA Astrophysics Data System (ADS)

    Chen, Wei R.; Nordquist, Robert E.

    1998-08-01

    Malignant tumors kill hosts almost entirely by tumor invasion to multiple sites including vital organs. These metastases are often difficult to detect and when detected it is usually too late for effective treatment. Therefore, control of metastatic tumors is by far the biggest challenge in cancer treatment. Can the metastases be prevented or eradicated by a treatment of local tumor that can be easily detected and treated? It apparently requires a systemic reaction, usually a tumor- specific immune response. Laser immunotherapy, a novel approach using laser, photosensitizer and immunoadjuvant, has shown the potential to achieve such an immune reaction. This new method was applied in treatment of rat metastatic mammary tumors. The tumor model is DMBA-4, an aggressive tumor that invades different sites through blood vessels and lymphatics. Without treatment, all the tumor-bearing rats died with an average survival time of less than 35 days. Remote metastases were observed in all late-stage tumor-bearing rats. Laser immunotherapy was capable of eradicating treated primary tumors, and more importantly, the metastases at remote sites were also eradicated without direct treatment. The probable mechanism is an induced tumor-specific immune response, and this hypothesis has been supported by several immunoassays. This new therapy may prove to be an effective treatment modality for metastatic tumors by a non-invasive local laser application.

  5. Sox10 expression in ovarian epithelial tumors is associated with poor overall survival.

    PubMed

    Kwon, Ah-Young; Heo, Ilyeong; Lee, Hye Jin; Kim, Gwangil; Kang, Haeyoun; Heo, Jin-Hyung; Kim, Tae Hoen; An, Hee Jung

    2016-05-01

    Sox10 is a transcription factor regulating the development of several cell lineages and is involved in tumor development. However, the clinicopathological relevance of Sox10 expression in ovarian cancer has not been examined. We assessed expression of Sox10 in ovarian epithelial tumors by immunohistochemistry and assessed its prognostic value by analyzing the correlation between its expression and clinicopathological factors. We used tissue microarrays including 244 ovarian epithelial tumors. Sox10 staining was found in the cytoplasm or nucleus of tumor cells. Malignant serous, mucinous, and endometrioid tumors were significantly more likely to express Sox10 than benign and borderline tumors. Expression patterns in adenocarcinomas were different for histologic subtypes: nuclear Sox10 staining was common in clear-cell adenocarcinomas and serous adenocarcinomas, whereas all cases of mucinous and endometrioid tumors were negative for nuclear staining. Nuclear Sox10 staining was also associated with chemoresistance and shorter overall survival in ovarian adenocarcinomas, notably in high-grade serous adenocarcinoma. Sox10 is expressed in many ovarian carcinomas, suggesting that it might be involved in oncogenesis of ovarian carcinoma. Expression pattern of Sox10 differs between histological subtypes. Nuclear Sox10 expression is an independent indicator of poor prognosis in ovarian adenocarcinomas, notably in high-grade serous adenocarcinomas. PMID:26951260

  6. Alvespimycin Hydrochloride in Treating Patients With Metastatic or Unresectable Solid Tumors

    ClinicalTrials.gov

    2013-04-09

    and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Adenoid Cystic Carcinoma of the Oral Cavity; Stage IV Basal Cell Carcinoma of the Lip; Stage IV Breast Cancer; Stage IV Colon Cancer; Stage IV Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage IV Gastric Cancer; Stage IV Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage IV Lymphoepithelioma of the Nasopharynx; Stage IV Lymphoepithelioma of the Oropharynx; Stage IV Melanoma; Stage IV Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Stage IV Mucoepidermoid Carcinoma of the Oral Cavity; Stage IV Ovarian Epithelial Cancer; Stage IV Prostate Cancer; Stage IV Renal Cell Cancer; Stage IV Salivary Gland Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IV Verrucous Carcinoma of the Larynx; Stage IV Verrucous Carcinoma of the Oral Cavity; Unspecified Adult Solid Tumor, Protocol Specific; Untreated Metastatic Squamous Neck Cancer With Occult Primary

  7. Metastatic cystosarcoma phylloides in an adolescent girl: an unusually malignant tumor.

    PubMed

    Hoover, H C; Trestioreanu, A; Ketcham, A S

    1975-03-01

    The first case of metastatic cystosarcoma phylloides in an adolescent is reported. This case also represents the first reported response of this tumor to chemotherapy and irradiation. This tumor showed an unusually rapid rate of cell division probably making it more susceptible to these agents. The importance of an early diagnosis and definitive excision is stressed. PMID:165788

  8. Frequency of mutations and polymorphisms in borderline ovarian tumors of known cancer genes.

    PubMed

    Stemke-Hale, Katherine; Shipman, Kristy; Kitsou-Mylona, Isidora; de Castro, David G; Hird, Vicky; Brown, Robert; Flanagan, James; Gabra, Hani; Mills, Gordon B; Agarwal, Roshan; El-Bahrawy, Mona

    2013-04-01

    Borderline ovarian tumors represent an understudied subset of ovarian tumors. Most studies investigating aberrations in borderline tumors have focused on KRAS/BRAF mutations. In this study, we conducted an extensive analysis of mutations and single-nucleotide polymorphisms (SNPs) in borderline ovarian tumors. Using the Sequenom MassArray platform, we investigated 160 mutations/polymorphisms in 33 genes involved in cell signaling, apoptosis, angiogenesis, cell cycle regulation and cellular senescence. Of 52 tumors analyzed, 33 were serous, 18 mucinous and 1 endometrioid. KRAS c.35G>A p.Gly12Asp mutations were detected in eight tumors (six serous and two mucinous), BRAF V600E mutations in two serous tumors, and PIK3CA H1047Y and PIK3CA E542K mutations in a serous and an endometrioid BOT, respectively. CTNNB1 mutation was detected in a serous tumor. Potentially functional polymorphisms were found in vascular endothelial growth factor (VEGF), ABCB1, FGFR2 and PHLPP2. VEGF polymorphisms were the most common and detected at four loci. PHLPP2 polymorphisms were more frequent in mucinous as compared with serous tumors (P=0.04), with allelic imbalance in one case. This study represents the largest and most comprehensive analysis of mutations and functional SNPs in borderline ovarian tumors to date. At least 25% of borderline ovarian tumors harbor somatic mutations associated with potential response to targeted therapeutics. PMID:23174937

  9. Frequency of mutations and polymorphisms in borderline ovarian tumors of known cancer genes

    PubMed Central

    Stemke-Hale, Katherine; Shipman, Kristy; Kitsou-Mylona, Isidora; de Castro, David Gonzalez; Hird, Vicky; Brown, Robert; Flanagan, James; Hani Gabra, H; Mills, Gordon B.; Agarwal, R; El-Bahrawy, Mona

    2013-01-01

    Borderline ovarian tumors represent an understudied subset of ovarian tumors. Most studies investigating aberrations in borderline tumors have focused on KRAS/BRAF mutations. In this study we conducted an extensive analysis of mutations and single nucleotide polymorphisms in borderline ovarian tumors. Using the Sequenom MassARRAY platform we investigated 160 mutations/polymorphisms in 33 genes involved in cell signalling, apoptosis, angiogenesis, cell cycle regulation, and cellular senescence. Of 52 tumors analysed, 33 were serous, 18 mucinous and 1 endometrioid. KRAS c.35G>A p.Gly12Asp mutations were detected in 8 tumors (6 serous and 2 mucinous), BRAF V600E mutations in 2 serous tumors, and PIK3CA H1047Y and PIK3CA E542K mutations in a serous and an endometrioid BOT respectively. CTNNB1 mutation was detected in a serous tumor. Potentially functional polymorphisms were found in VEGF, ABCB1, FGFR2 and PHLPP2. VEGF polymorphisms were the most common and detected at 4 loci. PHLPP2 polymorphisms were more frequent in mucinous as compared to serous tumors (p=0.04), with allelic imbalance in one case. This study represents the largest and most comprehensive analysis of mutations and functional single nucleotide polymorphisms in borderline ovarian tumors to date. At least 25% of borderline ovarian tumors harbour somatic mutations associated with potential response to targeted therapeutics. PMID:23174937

  10. I-123 MIBG imaging of metastatic carcinoid tumor from the rectum.

    PubMed

    Watanabe, N; Seto, H; Ishiki, M; Shimizu, M; Kageyama, M; Wu, Y W; Nagayoshi, T; Kamisaki, Y; Kakishita, M

    1995-04-01

    I-131 MIBG, a specific radiopharmaceutical agent for scintigraphic imaging and treatment of pheochromocytoma and neuroblastoma may be useful for detection of apudomas. Scintigraphy with I-123 radiolabeled MIBG was performed in a patient with metastatic carcinoid tumor from the rectum. I-123 MIBG scintigraphic findings showed multiple areas of abnormal tumor uptake of hepatic and bone metastases from the rectal carcinoid. Bone scintigraphy demonstrated multiple metastatic lesions. Computed tomography revealed multiple solid tumors of the liver. This report describes accumulation of I-123 MIBG in the liver and bone metastases from the rectal carcinoid. Radioiodine MIBG scintigraphy may be useful for detecting metastatic lesions, for evaluating postoperative recurrence, and also for the treatment of the carcinoid tumor. PMID:7788995

  11. Optical Detection and Virotherapy of Live Metastatic Tumor Cells in Body Fluids with Vaccinia Strains

    PubMed Central

    Minev, Boris R.; Zimmermann, Martina; Aguilar, Richard J.; Zhang, Qian; Sturm, Julia B.; Fend, Falko; Yu, Yong A.; Cappello, Joseph; Lauer, Ulrich M.; Szalay, Aladar A.

    2013-01-01

    Metastatic tumor cells in body fluids are important targets for treatment, and critical surrogate markers for evaluating cancer prognosis and therapeutic response. Here we report, for the first time, that live metastatic tumor cells in blood samples from mice bearing human tumor xenografts and in blood and cerebrospinal fluid samples from patients with cancer were successfully detected using a tumor cell-specific recombinant vaccinia virus (VACV). In contrast to the FDA-approved CellSearch system, VACV detects circulating tumor cells (CTCs) in a cancer biomarker-independent manner, thus, free of any bias related to the use of antibodies, and can be potentially a universal system for detection of live CTCs of any tumor type, not limited to CTCs of epithelial origin. Furthermore, we demonstrate for the first time that VACV was effective in preventing and reducing circulating tumor cells in mice bearing human tumor xenografts. Importantly, a single intra-peritoneal delivery of VACV resulted in a dramatic decline in the number of tumor cells in the ascitic fluid from a patient with gastric cancer. Taken together, these results suggest VACV to be a useful tool for quantitative detection of live tumor cells in liquid biopsies as well as a potentially effective treatment for reducing or eliminating live tumor cells in body fluids of patients with metastatic disease. PMID:24019862

  12. Extratumoral Heme Oxygenase-1 (HO-1) Expressing Macrophages Likely Promote Primary and Metastatic Prostate Tumor Growth

    PubMed Central

    Adamo, Hanibal; Thysell, Elin; Jernberg, Emma; Stattin, Pär; Widmark, Anders; Wikström, Pernilla; Bergh, Anders

    2016-01-01

    Aggressive tumors induce tumor-supporting changes in the benign parts of the prostate. One factor that has increased expression outside prostate tumors is hemoxygenase-1 (HO-1). To investigate HO-1 expression in more detail, we analyzed samples of tumor tissue and peritumoral normal prostate tissue from rats carrying cancers with different metastatic capacity, and human prostate cancer tissue samples from primary tumors and bone metastases. In rat prostate tumor samples, immunohistochemistry and quantitative RT-PCR showed that the main site of HO-1 synthesis was HO-1+ macrophages that accumulated in the tumor-bearing organ, and at the tumor-invasive front. Small metastatic tumors were considerably more effective in attracting HO-1+ macrophages than larger non-metastatic ones. In clinical samples, accumulation of HO-1+ macrophages was seen at the tumor invasive front, almost exclusively in high-grade tumors, and it correlated with the presence of bone metastases. HO-1+ macrophages, located at the tumor invasive front, were more abundant in bone metastases than in primary tumors. HO-1 expression in bone metastases was variable, and positively correlated with the expression of macrophage markers but negatively correlated with androgen receptor expression, suggesting that elevated HO-1 could be a marker for a subgroup of bone metastases. Together with another recent observation showing that selective knockout of HO-1 in macrophages reduced prostate tumor growth and metastatic capacity in animals, the results of this study suggest that extratumoral HO-1+ macrophages may have an important role in prostate cancer. PMID:27280718

  13. Extratumoral Heme Oxygenase-1 (HO-1) Expressing Macrophages Likely Promote Primary and Metastatic Prostate Tumor Growth.

    PubMed

    Halin Bergström, Sofia; Nilsson, Maria; Adamo, Hanibal; Thysell, Elin; Jernberg, Emma; Stattin, Pär; Widmark, Anders; Wikström, Pernilla; Bergh, Anders

    2016-01-01

    Aggressive tumors induce tumor-supporting changes in the benign parts of the prostate. One factor that has increased expression outside prostate tumors is hemoxygenase-1 (HO-1). To investigate HO-1 expression in more detail, we analyzed samples of tumor tissue and peritumoral normal prostate tissue from rats carrying cancers with different metastatic capacity, and human prostate cancer tissue samples from primary tumors and bone metastases. In rat prostate tumor samples, immunohistochemistry and quantitative RT-PCR showed that the main site of HO-1 synthesis was HO-1+ macrophages that accumulated in the tumor-bearing organ, and at the tumor-invasive front. Small metastatic tumors were considerably more effective in attracting HO-1+ macrophages than larger non-metastatic ones. In clinical samples, accumulation of HO-1+ macrophages was seen at the tumor invasive front, almost exclusively in high-grade tumors, and it correlated with the presence of bone metastases. HO-1+ macrophages, located at the tumor invasive front, were more abundant in bone metastases than in primary tumors. HO-1 expression in bone metastases was variable, and positively correlated with the expression of macrophage markers but negatively correlated with androgen receptor expression, suggesting that elevated HO-1 could be a marker for a subgroup of bone metastases. Together with another recent observation showing that selective knockout of HO-1 in macrophages reduced prostate tumor growth and metastatic capacity in animals, the results of this study suggest that extratumoral HO-1+ macrophages may have an important role in prostate cancer. PMID:27280718

  14. Clinical Significance of Tumor-Associated Inflammatory Cells in Metastatic Neuroblastoma

    PubMed Central

    Asgharzadeh, Shahab; Salo, Jill A.; Ji, Lingyun; Oberthuer, André; Fischer, Matthias; Berthold, Frank; Hadjidaniel, Michael; Liu, Cathy Wei-Yao; Metelitsa, Leonid S.; Pique-Regi, Roger; Wakamatsu, Peter; Villablanca, Judith G.; Kreissman, Susan G.; Matthay, Katherine K.; Shimada, Hiroyuki; London, Wendy B.; Sposto, Richard; Seeger, Robert C.

    2012-01-01

    Purpose Children diagnosed at age ≥ 18 months with metastatic MYCN-nonamplified neuroblastoma (NBL-NA) are at high risk for disease relapse, whereas those diagnosed at age < 18 months are nearly always cured. In this study, we investigated the hypothesis that expression of genes related to tumor-associated inflammatory cells correlates with the observed differences in survival by age at diagnosis and contributes to a prognostic signature. Methods Tumor-associated macrophages (TAMs) in localized and metastatic neuroblastomas (n = 71) were assessed by immunohistochemistry. Expression of 44 genes representing tumor and inflammatory cells was quantified in 133 metastatic NBL-NAs to assess age-dependent expression and to develop a logistic regression model to provide low- and high-risk scores for predicting progression-free survival (PFS). Tumors from high-risk patients enrolled onto two additional studies (n = 91) served as independent validation cohorts. Results Metastatic neuroblastomas had higher infiltration of TAMs than locoregional tumors, and metastatic tumors diagnosed in patients at age ≥ 18 months had higher expression of inflammation-related genes than those in patients diagnosed at age < 18 months. Expression of genes representing TAMs (CD33/CD16/IL6R/IL10/FCGR3) contributed to 25% of the accuracy of a novel 14-gene tumor classification score. PFS at 5 years for children diagnosed at age ≥ 18 months with NBL-NA with a low- versus high-risk score was 47% versus 12%, 57% versus 8%, and 50% versus 20% in three independent clinical trials, respectively. Conclusion These data suggest that interactions between tumor and inflammatory cells may contribute to the clinical metastatic neuroblastoma phenotype, improve prognostication, and reveal novel therapeutic targets. PMID:22927533

  15. Metastatic tumor: the complementary role of the marrow aspirate and biopsy.

    PubMed

    Atac, B; Lawrence, C; Goldberg, S N

    1991-10-01

    To determine whether bone marrow aspiration or biopsy is more sensitive in the detection of nonhematologic metastatic involvement of marrow, all 1569 consecutive paired biopsy and aspirate samples obtained between January 1975 and January 1, 1986 in an 800 bed municipal hospital were reviewed. At least eight aspirate slides and 10 biopsy cross sections were examined for each pair. In 39 samples, both biopsy and aspirate identified metastatic tumor. No biopsies contained tumor that was not also seen on the aspirate. However, five aspirate slides contained metastatic malignancies not identified on biopsy. The hematologist or oncologist viewing individual cells in a monolayer at 1000 x magnification has the advantage of identifying very small clusters of tumor cells. That accounted for three of the five positive aspirate samples in which the biopsies were negative. The other two positive aspirate slides each contained tumor on only one of eight slides. The results of our study indicate that when carefully reviewed, the aspirate is at least as sensitive as the marrow biopsy for identifying metastatic tumor. Our results indicate that marrow aspirates and biopsies are useful and complementary examinations for identifying metastatic malignancy. PMID:1928232

  16. Vorinostat in Combination With Paclitaxel and Carboplatin in Treating Patients With Metastatic or Recurrent Solid Tumors and HIV Infection

    ClinicalTrials.gov

    2016-08-03

    HIV Infection; Recurrent Anal Cancer; Recurrent Breast Cancer; Recurrent Esophageal Cancer; Recurrent Gastric Cancer; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage IV Anal Cancer; Stage IV Breast Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Salivary Gland Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IV Verrucous Carcinoma of the Larynx; Stage IV Verrucous Carcinoma of the Oral Cavity; Unspecified Adult Solid Tumor, Protocol Specific

  17. Tumor cells disseminate early, but immunosurveillance limits metastatic outgrowth, in a mouse model of melanoma

    PubMed Central

    Eyles, Jo; Puaux, Anne-Laure; Wang, Xiaojie; Toh, Benjamin; Prakash, Celine; Hong, Michelle; Tan, Tze Guan; Zheng, Lin; Ong, Lai Chun; Jin, Yi; Kato, Masashi; Prévost-Blondel, Armelle; Chow, Pierce; Yang, Henry; Abastado, Jean-Pierre

    2010-01-01

    Although metastasis is the leading cause of cancer-related death, it is not clear why some patients with localized cancer develop metastatic disease after complete resection of their primary tumor. Such relapses have been attributed to tumor cells that disseminate early and remain dormant for prolonged periods of time; however, little is known about the control of these disseminated tumor cells. Here, we have used a spontaneous mouse model of melanoma to investigate tumor cell dissemination and immune control of metastatic outgrowth. Tumor cells were found to disseminate throughout the body early in development of the primary tumor, even before it became clinically detectable. The disseminated tumor cells remained dormant for varying periods of time depending on the tissue, resulting in staggered metastatic outgrowth. Dormancy in the lung was associated with reduced proliferation of the disseminated tumor cells relative to the primary tumor. This was mediated, at least in part, by cytostatic CD8+ T cells, since depletion of these cells resulted in faster outgrowth of visceral metastases. Our findings predict that immune responses favoring dormancy of disseminated tumor cells, which we propose to be the seed of subsequent macroscopic metastases, are essential for prolonging the survival of early stage cancer patients and suggest that therapeutic strategies designed to reinforce such immune responses may produce marked benefits in these patients. PMID:20501944

  18. Combination Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Stage III Ovarian Cancer

    ClinicalTrials.gov

    2016-03-17

    Malignant Ovarian Mixed Epithelial Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Primary Peritoneal Carcinoma; Stage III Ovarian Cancer; Undifferentiated Ovarian Carcinoma

  19. Veliparib, Capecitabine, and Temozolomide in Patients With Advanced, Metastatic, and Recurrent Neuroendocrine Tumor

    ClinicalTrials.gov

    2016-07-10

    Functional Pancreatic Neuroendocrine Tumor; Malignant Somatostatinoma; Merkel Cell Carcinoma; Metastatic Adrenal Gland Pheochromocytoma; Metastatic Carcinoid Tumor; Multiple Endocrine Neoplasia Type 1; Multiple Endocrine Neoplasia Type 2A; Multiple Endocrine Neoplasia Type 2B; Neuroendocrine Neoplasm; Non-Functional Pancreatic Neuroendocrine Tumor; Pancreatic Glucagonoma; Pancreatic Insulinoma; Recurrent Adrenal Cortex Carcinoma; Recurrent Adrenal Gland Pheochromocytoma; Recurrent Merkel Cell Carcinoma; Somatostatin-Producing Neuroendocrine Tumor; Stage III Adrenal Cortex Carcinoma; Stage III Thyroid Gland Medullary Carcinoma; Stage IIIA Merkel Cell Carcinoma; Stage IIIB Merkel Cell Carcinoma; Stage IV Adrenal Cortex Carcinoma; Stage IV Merkel Cell Carcinoma; Stage IVA Thyroid Gland Medullary Carcinoma; Stage IVB Thyroid Gland Medullary Carcinoma; Stage IVC Thyroid Gland Medullary Carcinoma; Thymic Carcinoid Tumor; VIP-Producing Neuroendocrine Tumor; Well Differentiated Adrenal Cortex Carcinoma; Zollinger Ellison Syndrome

  20. Synergistic anti-tumor effects of zoledronic acid and radiotherapy against metastatic hepatocellular carcinoma.

    PubMed

    Morii, Kazuhiko; Aoyama, Yuhki; Nakamura, Shinichiro; Okushin, Hiroaki

    2015-01-01

    A 72-year-old man with advanced hepatocellular carcinoma and decompensated hepatitis C virus-related cirrhosis suffered from a metastatic femoral fracture. After undergoing radiotherapy, he was only treated with supportive care, except for the administration of zoledronic acid (ZA). Thereafter, the initially elevated serum α-fetoprotein and des-gamma carboxyprothrombin levels declined to within the normal ranges. Hepatic and metastatic adrenal tumors, distant from the radiation field, exhibited a surprising regression. ZA is known to inhibit the activity of osteoclasts, bone-residential macrophages, and has been reported to have a direct anti-tumor effect. ZA may adjust the immunological milieu in tumor microenvironments by inhibiting the tumor-associated macrophages. Because radiotherapy can enhance the presentation of tumor-associated antigens, ZA and radiotherapy may exert synergistic anti-tumor effects. PMID:26466697

  1. Head and Neck Metastatic Tumors: a Retrospective Survey of Iranian Patients

    PubMed Central

    Sadri, Donia; Azizi, Arash; Farhadi, Sareh; Shokrgozar, Hojjat; Entezari, Navid

    2015-01-01

    Statement of the Problem The head and neck region is an uncommon site for metastatic involvement, but it can be the first and only symptom of primary cancer. The incidence of these tumors and their primary origins are limited in Iranian patients. Purpose Therefore, this retrospective study aimed to investigate the frequency and the common related clinical manifestations, as well as, the most common types of cancers and the prevalent sites of the primary tumor. Materials and Method All medical records related to patients with history of head and neck tumors between 1991 and 2011 at Iran Cancer Institute were evaluated and the essential information was statistically analyzed. Results Sixty cases of cervical lymph node metastasis (0.36%) and 26 cases of head and neck metastatic tumors (0.16%) including 17 cases of distant cancer (0.10%) were recorded among all 16232 registered cancers. Out of all distant head and neck metastatic tumors, 4 cases were related to oral and maxillofacial area. Pain, swelling of neck, oral mucosa ulcer and dryness were the chief complaints. Squamous cell carcinoma and adenocarcinoma were the most frequent types of cancers. The most common metastatic sites were cervical musculature, scalp and parotid gland, and the most prevalent sites of primary tumor in females were breast and lung in males. Conclusion According to these cases, the incidence rate of head and neck metastatic tumors seems to be low. However, feasible similarity of clinical presentation of oral metastatic lesions to benign lesions might result in misdiagnosis. Hence, biopsy is mandatory in any case with unusual clinical presentation, especially in patients with a known malignant disease. PMID:25759853

  2. Locomotor proteins in tissues of primary tumors and metastases of ovarian and breast cancer

    NASA Astrophysics Data System (ADS)

    Kondakova, I. V.; Yunusova, N. V.; Spirina, L. V.; Shashova, E. E.; Kolegova, E. S.; Kolomiets, L. A.; Slonimskaya, E. M.; Villert, A. B.

    2016-08-01

    The paper discusses the capability for active movement in an extracellular matrix, wherein remodeling of the cytoskeleton by actin binding proteins plays a significant role in metastases formation. We studied the expression of actin binding proteins and β-catenin in tissues of primary tumors and metastases of ovarian and breast cancer. Contents of p45 Ser β-catenin and the actin severing protein gelsolin were decreased in metastases of ovarian cancer relative to primary tumors. The level of the cofilin, functionally similar to gelsolin, was significantly higher in metastases compared to primary ovarian and breast tumor tissue. In breast cancer, significant increase in the number of an actin monomer binder protein thymosin-β4 was observed in metastases as compared to primary tumors. The data obtained suggest the involvement of locomotor proteins in metastases formation in ovarian and breast cancer.

  3. Inhibition of metastatic tumor growth by targeted delivery of antioxidant enzymes.

    PubMed

    Nishikawa, Makiya; Hyoudou, Kenji; Kobayashi, Yuki; Umeyama, Yukari; Takakura, Yoshinobu; Hashida, Mitsuru

    2005-12-01

    To develop effective anti-metastatic therapy, targeted or sustained delivery of catalase was examined in mice. We found that mouse lung with metastatic colonies of adenocarcinoma colon26 cells exhibited reduced catalase activity. The interaction of the tumor cells with macrophages or hepatocytes generated detectable amounts of ROS, and increased the activity of matrix metalloproteinases. Hepatocyte-targeted delivery of catalase was successfully achieved by galactosylation, which was highly effective in inhibiting the hepatic metastasis of colon26 cells. PEGylation, which increased the retention of catalase in the circulation, effectively inhibited the pulmonary metastasis of the cells. To examine which processes in tumor metastasis are inhibited by catalase derivatives, the tissue distribution and proliferation of tumor cells in mice was quantitatively analyzed using firefly luciferase-expressing tumor cells. An injection of PEG-catalase just before the inoculation of melanoma B16-BL6/Luc cells significantly reduced the number of the tumor cells in the lung at 24 h. Daily dosing of PEG-catalase greatly inhibited the proliferation of the tumor cells, and increased the survival rate of the tumor-bearing mice. These results indicate that targeted or sustained delivery of catalase to sites where tumor cells metastasize is a promising approach for inhibiting metastatic tumor growth. PMID:16256238

  4. Multilocular peritoneal inclusion cyst mimicking an ovarian tumor: A case report

    PubMed Central

    Singh, Anju; Sehgal, Alka; Mohan, Harsh

    2015-01-01

    Peritoneal inclusion cysts are uncommon abdominopelvic cysts seen in perimenopausal women. It is often misdiagnosed clinically as an ovarian tumor due to similar presentation and mimicking findings on radiology. We describe a perimenopausal woman presenting with pelvic mass. Her clinical finding on radiology suggested an ovarian tumor; however, biopsy revealed it as peritoneal inclusion cysts. We discuss the possible ways to avoid such mistakes. PMID:25861208

  5. A Case of Metastatic Low-Grade Endometrial Stromal Sarcoma Treated with Letrozole after Ovarian Ablation by Radiotherapy

    PubMed Central

    Yang, Kyung Ho; Shin, Jung A; Jung, Joo Hyuk; Jung, Hae Won; Lee, Hye Ran; Chang, Sunhee; Park, Ji Yeon; Yi, Seong Yoon

    2015-01-01

    A 50-year-old woman was admitted to our hospital due to multiple lung nodules detected incidentally on a chest X-ray. A video-assisted thoracoscopic lung biopsy revealed low-grade endometrial stromal sarcoma (LG-ESS). She had undergone a simple hysterectomy 1 year earlier owing to a diagnosis of adenomyosis. A review of her previous hysterectomy specimen showed not endometriosis but LG-ESS. According to the patient’s levels of serum follicle stimulating hormone and estradiol, she was in the premenopausal state with retained and normally functioning ovaries. She then underwent ovarian ablation by radiotherapy, after which she was administered 2.5 mg of letrozole once per day. Three months later, the size of the metastatic nodules in both lungs had decreased. The patient was followed up for 24 months while continuing on letrozole, and maintained a partial remission. We report herein on a case of metastatic LG-ESS treated with letrozole after ovarian ablation by radiotherapy. PMID:25715770

  6. Safety and efficacy of carmustine (BCNU) wafers for metastatic brain tumors

    PubMed Central

    Ene, Chibawanye I.; Nerva, John D.; Morton, Ryan P.; Barkley, Ariana S.; Barber, Jason K.; Ko, Andrew L.; Silbergeld, Daniel L.

    2016-01-01

    Background: Carmustine (BCNU) wafers (Gliadel) prolongs local disease control and progression-free survival (PFS) in patients with malignant gliomas. However, in metastatic brain tumors, there is a paucity of evidence in support of its safety and efficacy. The goal of this study was to assess the safety and efficacy of Gliadel wafers in patients with metastatic brain tumors. Methods: We retrospectively reviewed the University of Washington experience with Gliadel wafers for metastatic brain tumors between 2000 and 2015. Results: Gliadel wafers were used in 14 patients with metastatic brain tumors during the period reviewed. There were no postoperative seizures, strokes, or hemorrhages. There was one postoperative wound infection necessitating return to the operating room. The mean time to tumor progression (n = 7) and death (n = 5) after Gliadel wafer implantation was 2.5 and 2.9 years, respectively. Age was the only variable affecting PFS in patients receiving Gliadel wafers. Patients <53 years old (n = 7) had a PFS of 0.52 years, whereas patients >53 years old (n = 7) had a PFS of 4.29 years (P = 0.02). There was no significant difference in PFS in relation to presenting Karnofsky Performance Status (P = 0.26), number of brain metastasis (P = 0.82), tumor volume (P = 0.54), prior surgery (P = 0.57), or prior radiation (P = 0.41). There were no significant differences in the mean survival in relationship to any variable including age. Conclusions: BCNU wafers are a safe and a potentially efficacious adjunct to surgery and radiation for improving local disease control in metastatic brain tumors. Larger studies, however, are needed to examine overall efficacy and tumor specific efficacy. PMID:27217968

  7. Tumor Exosomal RNAs Promote Lung Pre-metastatic Niche Formation by Activating Alveolar Epithelial TLR3 to Recruit Neutrophils.

    PubMed

    Liu, Yanfang; Gu, Yan; Han, Yanmei; Zhang, Qian; Jiang, Zhengping; Zhang, Xiang; Huang, Bo; Xu, Xiaoqing; Zheng, Jianming; Cao, Xuetao

    2016-08-01

    The pre-metastatic niche educated by primary tumor-derived elements contributes to cancer metastasis. However, the role of host stromal cells in metastatic niche formation and organ-specific metastatic tropism is not clearly defined. Here, we demonstrate that lung epithelial cells are critical for initiating neutrophil recruitment and lung metastatic niche formation by sensing tumor exosomal RNAs via Toll-like receptor 3 (TLR3). TLR3-deficient mice show reduced lung metastasis in the spontaneous metastatic models. Mechanistically, primary tumor-derived exosomal RNAs, which are enriched in small nuclear RNAs, activate TLR3 in lung epithelial cells, consequently inducing chemokine secretion in the lung and promoting neutrophil recruitment. Identification of metastatic axis of tumor exosomal RNAs and host lung epithelial cell TLR3 activation provides potential targets to control cancer metastasis to the lung. PMID:27505671

  8. Administered activity and metastatic cure probability during radioimmunotherapy of ovarian cancer in nude mice with {sup 211}At-MX35 F(ab'){sub 2}

    SciTech Connect

    Elgqvist, Joergen . E-mail: jorgen.elgqvist@radfys.gu.se; Andersson, Hakan; Bernhardt, Peter; Baeck, Tom; Claesson, Ingela; Hultborn, Ragnar; Jensen, Holger; Johansson, Bengt R.; Lindegren, Sture; Olsson, Marita; Palm, Stig; Warnhammar, Elisabet; Jacobsson, Lars

    2006-11-15

    Purpose: To elucidate the therapeutic efficacy of {alpha}-radioimmunotherapy of ovarian cancer in mice. This study: (i) estimated the minimum required activity (MRA), giving a reasonable high therapeutic efficacy; and (ii) calculated the specific energy to tumor cell nuclei and the metastatic cure probability (MCP) using various assumptions regarding monoclonal-antibody (mAb) distribution in measured tumors. The study was performed using the {alpha}-particle emitter Astatine-211 ({sup 211}At) labeled to the mAb MX35 F(ab'){sub 2}. Methods and Materials: Animals were inoculated intraperitoneally with {approx}1 x 10{sup 7} cells of the cell line NIH:OVCAR-3. Four weeks later animals were treated with 25, 50, 100, or 200 kBq {sup 211}At-MX35 F(ab'){sub 2} (n = 74). Another group of animals was treated with a nonspecific mAb: 100 kBq {sup 211}At-Rituximab F(ab'){sub 2} (n = 18). Eight weeks after treatment the animals were sacrificed and presence of macro- and microscopic tumors and ascites was determined. An MCP model was developed and compared with the experimentally determined tumor-free fraction (TFF). Results: When treatment was given 4 weeks after cell inoculation, the TFFs were 25%, 22%, 50%, and 61% after treatment with 25, 50, 100, or 200 kBq {sup 211}At-MX35 F(ab'){sub 2}, respectively, the specific energy to irradiated cell nuclei varying between {approx}2 and {approx}400 Gy. Conclusion: As a significant increase in the therapeutic efficacy was observed between the activity levels of 50 and 100 kBq (TFF increase from 22% to 50%), the conclusion was that the MRA is {approx}100 kBq {sup 211}At-MX35 F(ab'){sub 2}. MCP was most consistent with the TFF when assuming a diffusion depth of 30 {mu}m of the mAbs in the tumors.

  9. Expression of AQP6 and AQP8 in epithelial ovarian tumor.

    PubMed

    Ma, Jiong; Zhou, Chunxia; Yang, Jianhua; Ding, Xiaoyan; Zhu, Yunshan; Chen, Xuejun

    2016-04-01

    Aquaporins (AQPs), the rapid transition pores for water molecules, play an important role in maintenance of intracellular water balance. Studies showed that AQPs were also involved in occurrence, development, invasion and metastasis of tumors. In this study, we aimed to explore the distribution and expression differences of aquaporin 6 (AQP6) and aquaporin 8 (AQP8) in epithelial ovarian tumors. The expression of AQP6 and AQP8 in 47 cases of epithelial ovarian tumors were measured by immunochemical technique and Western blotting. AQP6 was strongly expressed in benign ovarian tumors, but weak signal was shown in malignant tumors. The difference was not statistically significant (P > 0.05). Compared with serous adenoma and normal tissues, AQP6 expression in serous carcinoma was obviously decreased (P < 0.05). AQP8 expressions were both identified in benign and malignant tumors, but there was no significantly statistical difference (P > 0.05). For patients with large volume of malignant ascites (>1000 ml), AQP8 expression was increased (P < 0.05). AQP8 expression in malignant tumors was not related to different clinical stages, presence of lymphatic metastasis, and differentiation degrees (P > 0.05). These data showed that AQP6 and AQP8 had different expression degrees in epithelial ovarian tissues, which suggests that AQP6 and AQP8 may play certain roles in epithelial ovarian tumors. PMID:26779650

  10. Polyglutamate Paclitaxel and Carboplatin in Treating Patients With Ovarian Epithelial, Peritoneal, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2015-05-07

    Fallopian Tube Carcinoma; Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Primary Peritoneal Carcinoma; Stage III Ovarian Cancer; Stage IV Ovarian Cancer; Undifferentiated Ovarian Carcinoma

  11. CT imaging of ovarian yolk sac tumor with emphasis on differential diagnosis.

    PubMed

    Li, Yang-Kang; Zheng, Yu; Lin, Jian-Bang; Xu, Gui-Xiao; Cai, Ai-Qun; Zhou, Xiu-Guo; Zhang, Guo-Jun

    2015-01-01

    Ovarian yolk sac tumors (YSTs) are rare neoplasms. No radiological study has been done to compare the imaging findings between this type of tumor and other ovarian tumors. Here we analyzed the CT findings of 11 pathologically proven ovarian YSTs and compared their imaging findings with 18 other types of ovarian tumors in the same age range. Patient age, tumor size, tumor shape, ascites and metastasis of two groups did not differ significantly (P > 0.05). A mixed solid-cystic nature, intratumoral hemorrhage, marked enhancement and dilated intratumoral vessel of two groups differed significantly (P < 0.05). The area under the ROC curve of four significant CT features was 0.679, 0.707, 0.705, and 1.000, respectively. Multivariate logistic regression analysis identified two independent signs of YST: intratumoral hemorrhage and marked enhancement. Our results show that certain suggestive CT signs that may be valuable for improving the accuracy of imaging diagnosis of YST and may be helpful in distinguishing YST from other ovarian tumors. PMID:26074455

  12. Evaluation of the effects of hyaluronic acid-carboxymethyl cellulose barrier on ovarian tumor progression

    PubMed Central

    2014-01-01

    Background Hyaluronic acid is a prognostic factor in ovarian cancers. It is also a component of Hyaluronic Acid-Carboxymethyl Cellulose (HA-CMC) barrier, an anti-adhesion membrane widely used during abdominal surgeries in particular for ovarian carcinosis. 70% of patients who undergo ovarian surgery will relapse due to the persistence of cancer cells. This study’s objective was to determine the oncological risk from use of this material, in the presence of residual disease, despite the benefit gained by it decreasing post-surgical adhesions in order to provide an unambiguous assessment of its appropriateness for use in ovarian surgical management. Methods We assessed the effects of HA-CMC barrier on the in vitro proliferation of human ovarian tumor cell lines (OVCAR-3, IGROV-1 and SKOV-3). We next evaluated, in vivo in nude mice, the capacity of this biomaterial to regulate the tumor progression of subcutaneous and intraperitoneal models of ovarian tumor xenografts. Results We showed that HA-CMC barrier does not increase in vitro proliferation of ovarian cancer cell lines compared to control. In vivo, HA-CMC barrier presence with subcutaneous xenografts induced neither an increase in tumor volume nor cell proliferation (Ki67 and mitotic index). With the exception of an increased murine carcinosis score in peritoneum, the presence of HA-CMC barrier with intraperitoneal xenografts modified neither macro nor microscopic tumor growth. Finally, protein analysis of survival (Akt), proliferation (ERK) and adhesion (FAK) pathways highlighted no activation on the xenografts imputable to HA-CMC barrier. Conclusions For the most part, our results support the lack of tumor progression activation due to HA-CMC barrier. We conclude that the benefits gained from using HA-CMC barrier membrane during ovarian cancer surgeries seem to outweigh the potential oncological risks. PMID:24739440

  13. Molecular characterization of circulating tumor cells in ovarian cancer

    PubMed Central

    Kolostova, Katarina; Pinkas, Michael; Jakabova, Anna; Pospisilova, Eliska; Svobodova, Pavla; Spicka, Jan; Cegan, Martin; Matkowski, Rafal; Bobek, Vladimir

    2016-01-01

    The main focus of the study was to detect circulating tumor cells (CTCs) in ovarian cancer (OC) patients using a new methodological approach (MetaCellTM) which is based on size-dependent separation of CTCs and subsequent cytomorphological evaluation. Cytomorphological evaluation using vital fluorescence microscopy approach enables to use the captured cells for further RNA/DNA analysis. The cytomorphological analysis is then completed by gene expression analysis (GEA). GEA showed that relative expression of EPCAM is elevated in CTC-enriched fractions in comparison to the whole peripheral blood sample and that the expression grows with in vitro cultivation time. Comparison of the relative gene expression level in the group of peripheral blood samples and CTC-fraction samples confirmed a statistically significant difference for the following genes (p < 0.02): KRT7, WT1, EPCAM, MUC16, MUC1, KRT18 and KRT19. Thus, we suggest that the combination of the above listed genes could confirm CTCs presence in OC patients with higher specificity than when GEA tests are performed for one marker only. The GEA revealed two separate clusters identifying patients with or without CTCs. PMID:27293992

  14. Fertility drug use and risk of ovarian tumors: a debated clinical challenge.

    PubMed

    Gadducci, Angiolo; Guerrieri, Maria Elena; Genazzani, Andrea Riccardo

    2013-01-01

    Infertility itself increases the incidence of ovarian carcinoma, while the potential additional risk associated with the use of fertility drugs is still debated. In 1992, the cumulative analysis of 12 US case-control studies revealed that women who received ovulation-inducing drugs had approximately three-fold higher incidence of invasive ovarian carcinoma. Other investigations reported a lower increase of the risk of invasive carcinoma or borderline tumor of the ovary in women treated with these agents. Conversely, several other case-control or cohort studies failed to detect a significant correlation between fertility drug use and ovarian tumor risk in either parous or nulliparous women compared with untreated infertile women. Moreover neither the number of treatment cycles nor the type of drug used was associated with an increased risk in most studies. Incessant ovulation and excessive gonadotropin secretion have been long considered to play a major role in the development of ovarian carcinoma, and therefore fertility drugs, which raise the serum levels of gonadotropins and increase the chances of multiple ovulations, have been retained as a risk factor for this malignancy, However, the large majority of literature data as well as the new hypotheses on ovarian carcinogenesis appear to exclude a relevant impact of fertility drug use on the risk of ovarian tumors, and especially of high-grade invasive epithelial ovarian cancers. PMID:22946709

  15. Copy number and targeted mutational analysis reveals novel somatic events in metastatic prostate tumors.

    PubMed

    Robbins, Christiane M; Tembe, Waibov A; Baker, Angela; Sinari, Shripad; Moses, Tracy Y; Beckstrom-Sternberg, Stephen; Beckstrom-Sternberg, James; Barrett, Michael; Long, James; Chinnaiyan, Arul; Lowey, James; Suh, Edward; Pearson, John V; Craig, David W; Agus, David B; Pienta, Kenneth J; Carpten, John D

    2011-01-01

    Advanced prostate cancer can progress to systemic metastatic tumors, which are generally androgen insensitive and ultimately lethal. Here, we report a comprehensive genomic survey for somatic events in systemic metastatic prostate tumors using both high-resolution copy number analysis and targeted mutational survey of 3508 exons from 577 cancer-related genes using next generation sequencing. Focal homozygous deletions were detected at 8p22, 10q23.31, 13q13.1, 13q14.11, and 13q14.12. Key genes mapping within these deleted regions include PTEN, BRCA2, C13ORF15, and SIAH3. Focal high-level amplifications were detected at 5p13.2-p12, 14q21.1, 7q22.1, and Xq12. Key amplified genes mapping within these regions include SKP2, FOXA1, and AR. Furthermore, targeted mutational analysis of normal-tumor pairs has identified somatic mutations in genes known to be associated with prostate cancer including AR and TP53, but has also revealed novel somatic point mutations in genes including MTOR, BRCA2, ARHGEF12, and CHD5. Finally, in one patient where multiple independent metastatic tumors were available, we show common and divergent somatic alterations that occur at both the copy number and point mutation level, supporting a model for a common clonal progenitor with metastatic tumor-specific divergence. Our study represents a deep genomic analysis of advanced metastatic prostate tumors and has revealed candidate somatic alterations, possibly contributing to lethal prostate cancer. PMID:21147910

  16. Copy number and targeted mutational analysis reveals novel somatic events in metastatic prostate tumors

    PubMed Central

    Robbins, Christiane M.; Tembe, Waibov A.; Baker, Angela; Sinari, Shripad; Moses, Tracy Y.; Beckstrom-Sternberg, Stephen; Beckstrom-Sternberg, James; Barrett, Michael; Long, James; Chinnaiyan, Arul; Lowey, James; Suh, Edward; Pearson, John V.; Craig, David W.; Agus, David B.; Pienta, Kenneth J.; Carpten, John D.

    2011-01-01

    Advanced prostate cancer can progress to systemic metastatic tumors, which are generally androgen insensitive and ultimately lethal. Here, we report a comprehensive genomic survey for somatic events in systemic metastatic prostate tumors using both high-resolution copy number analysis and targeted mutational survey of 3508 exons from 577 cancer-related genes using next generation sequencing. Focal homozygous deletions were detected at 8p22, 10q23.31, 13q13.1, 13q14.11, and 13q14.12. Key genes mapping within these deleted regions include PTEN, BRCA2, C13ORF15, and SIAH3. Focal high-level amplifications were detected at 5p13.2-p12, 14q21.1, 7q22.1, and Xq12. Key amplified genes mapping within these regions include SKP2, FOXA1, and AR. Furthermore, targeted mutational analysis of normal-tumor pairs has identified somatic mutations in genes known to be associated with prostate cancer including AR and TP53, but has also revealed novel somatic point mutations in genes including MTOR, BRCA2, ARHGEF12, and CHD5. Finally, in one patient where multiple independent metastatic tumors were available, we show common and divergent somatic alterations that occur at both the copy number and point mutation level, supporting a model for a common clonal progenitor with metastatic tumor-specific divergence. Our study represents a deep genomic analysis of advanced metastatic prostate tumors and has revealed candidate somatic alterations, possibly contributing to lethal prostate cancer. PMID:21147910

  17. A metastatic glomus jugulare tumor. A temporal bone report

    SciTech Connect

    El Fiky, F.M.; Paparella, M.M.

    1984-01-01

    The clinicopathologic findings in the temporal bone of a patient with a highly malignant metastasizing glomus jugulare tumor are reported. The patient exhibited all the symptoms of primary malignant tumors of the ear, including facial paralysis, otorrhea, pain, hearing loss, tinnitus, dizziness, and vertigo. He was treated with cobalt irradiation followed by radium implant in the ear canal for a residual tumor; then a left-sided radical mastoidectomy was performed.

  18. Drug therapy in metastatic neuroendocrine tumors of the gastroenteropancreatic system.

    PubMed

    Faiss, S; Scherübl, H; Riecken, E O; Wiedenmann, B

    1996-01-01

    Successful treatment of neuroendocrine tumor disease of the gastroenteropancreatic system requires a multimodal approach. Radical tumor surgery is required before other therapies are initiated. So far, only surgery has proven to be curative. If surgical intervention is not possible or a tumor-free state cannot be achieved, biotherapy with the somatostatin analogues octreotide or lanreotide should then be preferably carried out in patients with functional tumors. Interferon-alpha can alternatively be given. In patients with gastrinoma, therapy with proton pump inhibitors (e.g., omeprazol) is the initial treatment of choice. In patients with nonfunctional tumors, indication for treatment is only given in cases of documented tumor progress. In case of progressive tumor disease or functionality under the above-mentioned therapies, treatment with somatostatin analogues can be intensified by dose escalation or alternatively by a combination therapy with interferon-alpha and a somatostatin analogue. On the basis of the less favorable response of neuroendocrine foregut tumors to biotherapy, chemotherapy should be initiated after failure of biotherapy in documented tumor progression. A combination of streptozotocin and 5-fluorouracil, possibly combined with D,L-folinic acid, is the treatment of choice, considering the response and side effect rates. In case of predominantly anaplastic neuroendocrine tumors in advanced stages, good tumor response rates with a chemotherapeutic scheme consisting of cisplatin and etoposide can be achieved. Since the chemotherapy scheme is less effective in patients with midgut or hindgut tumors, chemoembolization of liver metastases should follow biotherapy. The response to chemoembolization may be increased by simultaneous systemic chemotherapy. Attention should always be paid to an adequate analgesic drug administration. PMID:8893342

  19. Integrated imaging of hepatic tumors in childhood. Part I. Malignant lesions (primary and metastatic)

    SciTech Connect

    Miller, J.H.; Greenspan, B.S.

    1985-01-01

    Both the prognosis and treatment of hepatic tumors in children depend upon the histological diagnosis and the extent of disease. Recent advances in imaging techniques permit characterization of specific tumors and differentiation from other intrahepatic processes. An integrated imaging protocol involving a combination of ultrasound, computed tomography, and scintigraphy often provides a high degree of accuracy. Patterns derived from 40 cases of hepatoblastoma, hepatocellular carcinoma, rhabdomyosarcoma, monotypic small-cell sarcoma, and metastatic tumors are discussed and an algorithm for evaluation of hepatic tumors in children is presented.

  20. Laser immunotherapy: a novel approach for metastatic tumors

    NASA Astrophysics Data System (ADS)

    Chen, Wei R.; Korbelik, Mladen; Bartels, Kenneth E.; Liu, Hong; Nordquist, Robert E.

    2004-08-01

    The ideal treatment modality for tumors, particularly for those that metastasize to multiple remote sites, should eradicate the primary tumor and elicit a systemic, tumor-specific response leading to elimination of metastases and to long-term tumor immunity. Using the selective photothermal interaction as a precursor, laser immunotherapy was developed by introducing a novel immunoadjuvant administered in conjunction with the laser-absorbing dye. Specifically, an 805-nm laser and indocyanine green (ICG) was used for the selective photothermal interaction, and a novel immunoadjuvant, glycated chitosan (GC), was used as the immunological stimulant. The laser-ICG-GC combinations has been resulted in the following results in animal studies. (1) Selective destruction of deep target tumor target has been achieved; (2) Eradication of treated primary tumors and regression and disappearance of untreated distant metastases have been observed; (3) Long-term survival of tumor-bearing rats have been resulted; (4) Long-term immunity for resistance to repeated, dose-escalated subsequent tumor challenges has been induced; (5) Tumor-specific immunological responses, after laser immunotherapy treatment, have been detected at cellular and molecular levels. The procedure of laser immunotherapy and major results in animal studies will be summarized and some new results using the immunological enhancement for photodynamic therapy treatment will be presented.

  1. Solid Pseudopapillary Tumor of the Pancreas: One Case with a Metastatic Evolution in a Caucasian Woman

    PubMed Central

    Lestelle, Valentin; de Coster, Claire; Sarran, Anthony; Poizat, Flora; Delpero, Jean-Robert; Raoul, Jean-Luc

    2015-01-01

    We report the case of a Caucasian woman, operated on for a solid pseudopapillary tumor of the pancreas in 2009, who recurred 4 years later with multiple liver metastases requiring liver resection. This disease is infrequent, particularly among the Caucasian population, and metastatic evolution is very rare. PMID:26557078

  2. Solid Pseudopapillary Tumor of the Pancreas: One Case with a Metastatic Evolution in a Caucasian Woman.

    PubMed

    Lestelle, Valentin; de Coster, Claire; Sarran, Anthony; Poizat, Flora; Delpero, Jean-Robert; Raoul, Jean-Luc

    2015-01-01

    We report the case of a Caucasian woman, operated on for a solid pseudopapillary tumor of the pancreas in 2009, who recurred 4 years later with multiple liver metastases requiring liver resection. This disease is infrequent, particularly among the Caucasian population, and metastatic evolution is very rare. PMID:26557078

  3. Polymethylmethacrylate-augmented screw fixation for stabilization in metastatic spinal tumors. Technical note.

    PubMed

    Jang, Jee Soo; Lee, Sang Ho; Rhee, Chang Hun; Lee, Seung Hoon

    2002-01-01

    Screw fixation augmented with polymethylmethacrylate (PMMA) or some other biocompatible bone cement has been used in patients with osteoporosis requiring spinal fusion. No clinical studies have been conducted on PMMA-augmented screw fixation for stabilization of the vertebral column in patients with metastatic spinal tumors. The purpose of this study was to determine whether screw fixation augmented with PMMA might be suitable in patients treated for multilevel metastatic spinal tumors. Ten patients with metastatic spinal tumors involving multiple vertebral levels underwent stabilization procedures in which PMMA was used to augment screw fixation after decompression of the spinal cord. Within 15 days, partial or complete relief from pain was obtained in all patients postoperatively. Two of four patients in whom neurological deficits caused them to be nonambulatory before surgery were able to ambulate postoperatively. Neither collapse of the injected vertebral bodies nor failure of the screw fixation was observed during the mean follow-up period of 6.7 months. Screw fixation augmented with PMMA may offer stronger stabilization and facilitate the instrumentation across short segments in the treatment of multilevel metastatic spinal tumors. PMID:11795702

  4. FRIZZLED7 Is Required for Tumor Inititation and Metastatic Growth of Melanoma Cells

    PubMed Central

    Tiwary, Shweta; Xu, Lei

    2016-01-01

    Metastases are thought to arise from cancer stem cells and their tumor initiating abilities are required for the establishment of metastases. Nevertheless, in metastatic melanoma, the nature of cancer stem cells is under debate and their contribution to metastasis formation remains unknown. Using an experimental metastasis model, we discovered that high levels of the WNT receptor, FZD7, correlated with enhanced metastatic potentials of melanoma cell lines. Knocking down of FZD7 in a panel of four melanoma cell lines led to a significant reduction in lung metastases in animal models, arguing that FZD7 plays a causal role during metastasis formation. Notably, limiting dilution analyses revealed that FZD7 is essential for the tumor initiation of melanoma cells and FZD7 knockdown impeded the early expansion of metastatic melanoma cells shortly after seeding, in accordance with the view that tumor initiating ability of cancer cells is required for metastasis formation. FZD7 activated JNK in melanoma cell lines in vitro and the expression of a dominant negative JNK suppressed metastasis formation in vivo, suggesting that FZD7 may promote metastatic growth of melanoma cells via activation of JNK. Taken together, our findings uncovered a signaling pathway that regulates the tumor initiation of melanoma cells and contributes to metastasis formation in melanoma. PMID:26808375

  5. A rare cause in etiology of left atrial mass: metastatic testicular germ cell tumor

    PubMed Central

    Huseyin, Serhat; Okyay, Ahmet; Hacıbekiroğlu, İlhan; Tastekin, Ebru; Yılmaztepe, Mustafa; Taylan, Gökay; Canbaz, Suat; Çiçin, İrfan

    2016-01-01

    Although intracardiac metastasis of germ cell tumors is rare, it can be localized in the right or left heart by disseminating spread and give their cardiac symptoms depending on the location of metastatic mass. We present a 38-year-old male patient with a preliminary diagnosis of testicular tumor who was followed by the medical oncology clinic with cerebrovascular event and heart failure symptoms. PMID:27212979

  6. Metastatic cystosarcoma phylloides in an adolescent girl: an unusually malignant tumor.

    PubMed Central

    Hoover, H C; Trestioreanu, A; Ketcham, A S

    1975-01-01

    The first case of metastatic cystosarcoma phylloides in an adolescent is reported. This case also represents the first reported response of this tumor to chemotherapy and irradiation. This tumor showed an unusually rapid rate of cell division probably making it more susceptible to these agents. The importance of an early diagnosis and definitive excision is stressed. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. PMID:165788

  7. Primary ovarian neuroendocrine tumor arising in association with a mature cystic teratoma: A case report.

    PubMed

    Orsi, Nicolas M; Menon, Mini

    2016-08-01

    Primary ovarian carcinoid tumors are exceptionally rare entities accounting for approximately 0.1% of all ovarian neoplasms. This report describes a primary ovarian neuroendocrine tumor arising in association with a mature cystic teratoma in a 65 year-old woman. Macroscopically, the unilateral adnexal tumor was composed of cystic, solid and mucinous elements which resolved into a dual component lesion histologically. The majority of the tumor displayed an organoid architecture with mild to moderate pleomorphism and no discernible mitotic activity, while approximately 10% consisted of sheets and groups of cells with highly pleomorphic nuclei, necrosis and occasional mitoses. Features of a mature cystic teratoma were seen very focally. Immunohistochemistry revealed strong, diffuse positivity for CD56 and synaptophysin. Chromogranin immunonegativity was noted and there was an absence of nuclear β-catenin accumulation. Ki-67 index was 10-12%. Although there is no established diagnostic framework for primary ovarian carcinoid tumors, this case was diagnosed as a well-differentiated neuroendocrine tumor, Grade 2 (intermediate grade), arising in association with a mature cystic teratoma/dermoid cyst. This case highlights the need to develop ovarian diagnostic criteria in this area. PMID:27508272

  8. Evaluation and Management of Ultrasonographically Detected Ovarian Tumors in Asymptomatic Women.

    PubMed

    van Nagell, John Rensselaer; Miller, Rachel Ware

    2016-05-01

    Data from screening trials indicate that a significant percent of asymptomatic women older than 50 years of age will develop ovarian abnormalities that are detectable by ultrasonography. Most of these abnormalities are benign, and many will resolve spontaneously. However, the risk of ovarian cancer, particularly in postmenopausal women, is of concern. The goal is to use a diagnostic and treatment algorithm that will reliably detect ovarian cancer at the earliest possible stage while limiting the number of women undergoing surgery for benign disease. The combination of morphology indexing and serum biomarker analysis can accurately predict the risk of malignancy in most ovarian tumors. Ovarian tumors with cystic or septate morphology are at minimal risk of malignancy and can be followed with serial ultrasonography evaluations, thereby avoiding the morbidity and cost of surgery. Complex or solid ovarian tumors with a high morphology index score, or those with increasing biomarker production, are at a high risk of malignancy, and patients with these tumors should be referred to a gynecologic oncologist for further evaluation and treatment. PMID:27054927

  9. Tumor Phosphatidylinositol-3-Kinase Signaling and Development of Metastatic Disease in Locally Advanced Rectal Cancer

    PubMed Central

    Ree, Anne Hansen; Kristensen, Annette Torgunrud; Saelen, Marie Grøn; de Wijn, Rik; Edvardsen, Hege; Jovanovic, Jovana; Abrahamsen, Torveig Weum; Dueland, Svein; Flatmark, Kjersti

    2012-01-01

    Background Recognizing EGFR as key orchestrator of the metastatic process in colorectal cancer, but also the substantial heterogeneity of responses to anti-EGFR therapy, we examined the pattern of composite tumor kinase activities governed by EGFR-mediated signaling that might be implicated in development of metastatic disease. Patients and Methods Point mutations in KRAS, BRAF, and PIK3CA and ERBB2 amplification were determined in primary tumors from 63 patients with locally advanced rectal cancer scheduled for radical treatment. Using peptide arrays with tyrosine kinase substrates, ex vivo phosphopeptide profiles were generated from the same baseline tumor samples and correlated to metastasis-free survival. Results Unsupervised clustering analysis of the resulting phosphorylation of 102 array substrates defined two tumor classes, both consisting of cases with and without KRAS/BRAF mutations. The smaller cluster group of patients, with tumors generating high ex vivo phosphorylation of phosphatidylinositol-3-kinase-related substrates, had a particularly aggressive disease course, with almost a half of patients developing metastatic disease within one year of follow-up. Conclusion High phosphatidylinositol-3-kinase-mediated signaling activity of the primary tumor, rather than KRAS/BRAF mutation status, was identified as a hallmark of poor metastasis-free survival in patients with locally advanced rectal cancer undergoing radical treatment of the pelvic cavity. PMID:23226389

  10. The effect of Escherichia coli lipopolysaccharide and Tumor Necrosis Factor alpha on ovarian function

    PubMed Central

    Williams, Erin J.; Sibley, Kelly; Miller, Aleisha N.; Lane, Elizabeth A.; Fishwick, John; Nash, Deborah M.; Herath, Shan; England, Gary CW; Dobson, Hilary; Sheldon, I. Martin

    2009-01-01

    Problem Pelvic inflammatory disease and metritis are important causes of infertility in humans and domestic animals. Uterine infection with Escherichia coli in cattle is associated with reduced ovarian follicle growth and decreased estradiol secretion. We hypothesized that this effect could be mediated by the bacterial lipopolysaccharide (LPS) or cytokines such as tumor necrosis factor alpha (TNFα). Method of study In vitro, bovine ovarian theca and granulosa cells were treated with LPS or TNFα and steroid secretion measured. In vivo, the effect of LPS or TNFα intrauterine infusion was determined by ovarian ultrasonography and measurement of hormones in cattle. Results LPS reduced granulosa cell estradiol secretion, whilst TNFα decreased theca and granulosa cell androstenedione and estradiol production, respectively. In vivo, fewer animals ovulated following intrauterine infusion with LPS or TNFα. Conclusion LPS and TNFα suppress ovarian cell function, supporting the concept that pelvic inflammatory disease and metritis are detrimental for bovine ovarian health. PMID:19238751

  11. SIRT7 inactivation reverses metastatic phenotypes in epithelial and mesenchymal tumors

    PubMed Central

    Malik, Shivani; Villanova, Lidia; Tanaka, Shinji; Aonuma, Misato; Roy, Nilotpal; Berber, Elisabeth; Pollack, Jonathan R.; Michishita-Kioi, Eriko; Chua, Katrin F.

    2015-01-01

    Metastasis is responsible for over 90% of cancer-associated mortality. In epithelial carcinomas, a key process in metastatic progression is the epigenetic reprogramming of an epithelial-to-mesenchymal transition-like (EMT) change towards invasive cellular phenotypes. In non-epithelial cancers, different mechanisms must underlie metastatic change, but relatively little is known about the factors involved. Here, we identify the chromatin regulatory Sirtuin factor SIRT7 as a key regulator of metastatic phenotypes in both epithelial and mesenchymal cancer cells. In epithelial prostate carcinomas, high SIRT7 levels are associated with aggressive cancer phenotypes, metastatic disease, and poor patient prognosis, and depletion of SIRT7 can reprogram these cells to a less aggressive phenotype. Interestingly, SIRT7 is also important for maintaining the invasiveness and metastatic potential of non-epithelial sarcoma cells. Moreover, SIRT7 inactivation dramatically suppresses cancer cell metastasis in vivo, independent of changes in primary tumor growth. Mechanistically, we also uncover a novel link between SIRT7 and its family member SIRT1, providing the first demonstration of direct interaction and functional interplay between two mammalian sirtuins. Together with previous work, our findings highlight the broad role of SIRT7 in maintaining the metastatic cellular phenotype in diverse cancers. PMID:25923013

  12. Paired Tumor and Normal Whole Genome Sequencing of Metastatic Olfactory Neuroblastoma

    PubMed Central

    Weiss, Glen J.; Liang, Winnie S.; Izatt, Tyler; Arora, Shilpi; Cherni, Irene; Raju, Robert N.; Hostetter, Galen; Kurdoglu, Ahmet; Christoforides, Alexis; Sinari, Shripad; Baker, Angela S.; Metpally, Raghu; Tembe, Waibhav D.; Phillips, Lori

    2012-01-01

    Background Olfactory neuroblastoma (ONB) is a rare cancer of the sinonasal tract with little molecular characterization. We performed whole genome sequencing (WGS) on paired normal and tumor DNA from a patient with metastatic-ONB to identify the somatic alterations that might be drivers of tumorigenesis and/or metastatic progression. Methodology/Principal Findings Genomic DNA was isolated from fresh frozen tissue from a metastatic lesion and whole blood, followed by WGS at >30X depth, alignment and mapping, and mutation analyses. Sanger sequencing was used to confirm selected mutations. Sixty-two somatic short nucleotide variants (SNVs) and five deletions were identified inside coding regions, each causing a non-synonymous DNA sequence change. We selected seven SNVs and validated them by Sanger sequencing. In the metastatic ONB samples collected several months prior to WGS, all seven mutations were present. However, in the original surgical resection specimen (prior to evidence of metastatic disease), mutations in KDR, MYC, SIN3B, and NLRC4 genes were not present, suggesting that these were acquired with disease progression and/or as a result of post-treatment effects. Conclusions/Significance This work provides insight into the evolution of ONB cancer cells and provides a window into the more complex factors, including tumor clonality and multiple driver mutations. PMID:22649506

  13. Total enbloc spondylectomy for metastatic high grade spinal tumors: Early results

    PubMed Central

    Patil, Sanganagouda S; Nene, Abhay M

    2016-01-01

    Background: High grade metastatic spinal tumors are most common and are invasive. These patients can succumb to disease progression if not treated timely. Although considered as invasive and morbid, total enbloc spondylectomy (TES) in selected cases has better survival rates. The authors describe the results of TES for high grade metastatic spinal tumors. Materials and Methods: Five patients (four females and one male) underwent TES for solitary metastatic vertebral lesion between November 2012 and January 2014. These patients presented to us with spinal instability, unrelenting severe spinal pain and/or with severe progressive radiculopathy. Average age was 46.2 years (range 39–62 years). After complete investigations, computed tomography scan, magnetic resonance imaging scan and positron emission tomography (PET) scan, it was confirmed that these patients had high grade solitary vertebral metastatic tumor. Results: Average duration of followup was 18 months (range 16–20 months). The average preoperative visual analog scale score of 9.4 (range 9–10) improved to 2 (range 1–4) at last followup. Average blood loss was 1440 mL (range 1000–2000 mL). Average duration of surgery was 198 min (range 180–240 min). Significant pain relief was noticed in each patient in the immediate postoperative period and during followups. These patients attained complete functional activities of daily living with in a month. The imaging showed implants in situ, no recurrence of tumor, and no activity on PET scan at the final followup. Conclusion: The present series shows favorable short term results of TES for solitary, metastatic, high grade vertebral body tumors by a team approach. PMID:27512215

  14. Ovarian malignant germ cell tumors: cellular classification and clinical and imaging features.

    PubMed

    Shaaban, Akram M; Rezvani, Maryam; Elsayes, Khaled M; Baskin, Henry; Mourad, Amr; Foster, Bryan R; Jarboe, Elke A; Menias, Christine O

    2014-01-01

    Ovarian malignant germ cell tumors (OMGCTs) are heterogeneous tumors that are derived from the primitive germ cells of the embryonic gonad. OMGCTs are rare, accounting for about 2.6% of all ovarian malignancies, and typically manifest in adolescence, usually with abdominal pain, a palpable mass, and elevated serum tumor marker levels, which may serve as an adjunct in the initial diagnosis, monitoring during therapy, and posttreatment surveillance. Dysgerminoma, the most common malignant germ cell tumor, usually manifests as a solid mass. Immature teratomas manifest as a solid mass with scattered foci of fat and calcifications. Yolk sac tumors usually manifest as a mixed solid and cystic mass. Capsular rupture or the bright dot sign, a result of increased vascularity and the formation of small vascular aneurysms, may be present. Embryonal carcinomas and polyembryomas rarely manifest in a pure form and are more commonly part of a mixed germ cell tumor. Some OMGCTs have characteristic features that allow a diagnosis to be confidently made, whereas others have nonspecific features, which make them difficult to diagnose. However, imaging features, the patient's age at presentation, and tumor markers may help establish a reasonable differential diagnosis. Malignant ovarian germ cell tumors spread in the same manner as epithelial ovarian neoplasms but are more likely to involve regional lymph nodes. Preoperative imaging may depict local extension, peritoneal disease, and distant metastases. Suspicious areas may be sampled during surgery. Because OMGCTs are almost always unilateral and are chemosensitive, fertility-sparing surgery is the standard of care. PMID:24819795

  15. Ovarian carcinoma patient derived xenografts reproduce their tumor of origin and preserve an oligoclonal structure

    PubMed Central

    Colombo, Pierre-Emmanuel; du Manoir, Stanislas; Orsetti, Béatrice; Bras-Gonçalves, Rui; Lambros, Mario B.; MacKay, Alan; Nguyen, Tien-Tuan; Boissiére, Florence; Pourquier, Didier; Bibeau, Frédéric; Reis-Filho, Jorge S.; Theillet, Charles

    2015-01-01

    Advanced Epithelial Ovarian Cancer (EOC) patients frequently relapse by 24 months and develop resistant disease. Research on EOC therapies relies on cancer cell lines established decades ago making Patient Derived Xenografts (PDX) attractive models, because they are faithful representations of the original tumor. We established 35 ovarian cancer PDXs resulting from the original graft of 77 EOC samples onto immuno-compromised mice. PDXs covered the diversity of EOC histotypes and graft take was correlated with early patient death. Fourteen PDXs were characterized at the genetic and histological levels. PDXs reproduced phenotypic features of the ovarian tumors of origin and conserved the principal characteristics of the original copy number change (CNC) profiles over several passages. However, CNC fluctuations in specific subregions comparing the original tumor and the PDXs indicated the oligoclonal nature of the original tumors. Detailed analysis by CGH, FISH and exome sequencing of one case, for which several tumor nodules were sampled and grafted, revealed that PDXs globally maintained an oligoclonal structure. No overgrowth of a particular subclone present in the original tumor was observed in the PDXs. This suggested that xenotransplantation of ovarian tumors and growth as PDX preserved at least in part the clonal diversity of the original tumor. We believe our data reinforce the potential of PDX as exquisite tools in pre-clinical assays. PMID:26334103

  16. A Giant Ovarian Tumor Causing Anasarca and Dyspnea Successfully Managed after Preoperative Drainage.

    PubMed

    Yamaguchi, Munekage; Tashiro, Hironori; Takaishi, Kiyomi; Honda, Ritsuo; Katabuchi, Hidetaka

    2015-01-01

    Serious complications are likely to accompany the treatment of giant ovarian tumors, and resection with or without preoperative drainage has been previously reported. Here, we report the case of a 27-year-old Japanese woman with a significant weight gain of 50 kg, who was referred to the Kumamoto University Hospital because of gait impairment and dyspnea. Imaging tests revealed an ovarian tumor, 37 cm in diameter, with two solid components. The patient's condition improved after the removal of 31.5 l tumor fluid by using a suprapubic urinary catheter for 3 days. The tumor was subsequently resected without complications, and was diagnosed as a left mucinous ovarian tumor with malignant components, weighing 37 kg (81.5 lb). The patient was discharged after her anasarca improved, and her body weight decreased from 100 to 50 kg with accompanying considerable urination within two weeks. She was in good condition with no evidence of recurrence at 15 months after surgery. Tumor resection after preoperative drainage was effective in the management of a patient with dyspnea induced by a giant ovarian tumor. We suggest the use of a suprapubic urinary catheter for preoperative drainage because of its ease of use in preventing fluid leakage from the possibly malignant tumor. PMID:25661539

  17. Identification of Tumor Suppressors and Oncogenes from Genomic and Epigenetic Features in Ovarian Cancer

    PubMed Central

    Wrzeszczynski, Kazimierz O.; Varadan, Vinay; Byrnes, James; Lum, Elena; Kamalakaran, Sitharthan; Levine, Douglas A.; Dimitrova, Nevenka; Zhang, Michael Q.; Lucito, Robert

    2011-01-01

    The identification of genetic and epigenetic alterations from primary tumor cells has become a common method to identify genes critical to the development and progression of cancer. We seek to identify those genetic and epigenetic aberrations that have the most impact on gene function within the tumor. First, we perform a bioinformatic analysis of copy number variation (CNV) and DNA methylation covering the genetic landscape of ovarian cancer tumor cells. We separately examined CNV and DNA methylation for 42 primary serous ovarian cancer samples using MOMA-ROMA assays and 379 tumor samples analyzed by The Cancer Genome Atlas. We have identified 346 genes with significant deletions or amplifications among the tumor samples. Utilizing associated gene expression data we predict 156 genes with altered copy number and correlated changes in expression. Among these genes CCNE1, POP4, UQCRB, PHF20L1 and C19orf2 were identified within both data sets. We were specifically interested in copy number variation as our base genomic property in the prediction of tumor suppressors and oncogenes in the altered ovarian tumor. We therefore identify changes in DNA methylation and expression for all amplified and deleted genes. We statistically define tumor suppressor and oncogenic features for these modalities and perform a correlation analysis with expression. We predicted 611 potential oncogenes and tumor suppressors candidates by integrating these data types. Genes with a strong correlation for methylation dependent expression changes exhibited at varying copy number aberrations include CDCA8, ATAD2, CDKN2A, RAB25, AURKA, BOP1 and EIF2C3. We provide copy number variation and DNA methylation analysis for over 11,500 individual genes covering the genetic landscape of ovarian cancer tumors. We show the extent of genomic and epigenetic alterations for known tumor suppressors and oncogenes and also use these defined features to identify potential ovarian cancer gene candidates. PMID

  18. Passive Entrapment of Tumor Cells Determines Metastatic Dissemination to Spinal Bone and Other Osseous Tissues.

    PubMed

    Broggini, Thomas; Piffko, Andras; Hoffmann, Christian J; Harms, Christoph; Vajkoczy, Peter; Czabanka, Marcus

    2016-01-01

    During the metastatic process tumor cells circulate in the blood stream and are carried to various organs. In order to spread to different organs tumor cell-endothelial cell interactions are crucial for extravasation mechanisms. It remains unclear if tumor cell dissemination to the spinal bone occurs by passive entrapment of circulating tumor cells or by active cellular mechanisms mediated by cell surface molecules or secreted factors. We investigated the seeding of three different tumor cell lines (melanoma, lung and prostate carcinoma) to the microvasculature of different organs. Their dissemination was compared to biologically passive microbeads. The spine and other organs were resected three hours after intraarterial injection of tumor cells or microbeads. Ex vivo homogenization and fluorescence analysis allowed quantification of tumor cells or microbeads in different organs. Interestingly, tumor cell distribution to the spinal bone was comparable to dissemination of microbeads independent of the tumor cell type (melanoma: 5.646% ± 7.614%, lung: 6.007% ± 1.785%, prostate: 3.469% ± 0.602%, 7 μm beads: 9.884% ± 7.379%, 16 μm beads: 7.23% ± 1.488%). Tumor cell seeding differed significantly between tumor cells and microbeads in all soft tissue organs. Moreover, there were significant differences between the different tumor cell lines in their dissemination behaviour to soft tissue organs only. These findings demonstrate that metastatic dissemination of tumor cells to spinal bone and other osseous organs is mediated by passive entrapment of tumor cells similar to passive plugging of microvasculature observed after intraarterial microbeads injection. PMID:27603673

  19. Multiple brown tumors in parathyroid carcinoma mimicking metastatic bone disease.

    PubMed

    Pai, M; Park, C H; Kim, B S; Chung, Y S; Park, H B

    1997-10-01

    An unusual case of multiple brown tumors due to parathyroid carcinoma is reported. The patient presented with lower leg pain. Plain radiographs demonstrated multiple lytic lesions of the lower legs and a Tc-99m MDP bone scan depicted multiple areas of increased uptake suggesting skeletal metastases. Tc-99m sestamibi tumor scintigraphy showed multiple sites of tumor uptake in bones and a large area of increased uptake with a cystic component in the right lower pole of the thyroid gland. An open biopsy from the right tibial lesion revealed a brown tumor. A large parathyroid carcinoma with a necrotic cyst was removed. After parathyroidectomy and right thyroid lobectomy, the patient became free of bone pain and serum PTH levels normalized. A 9-month follow-up Tc-99m MDP bone scan demonstrated less intense uptake in the pelvis, tibia, and fibulae. Nine-month follow-up tumor imaging with Tc-99m MIBI revealed disappearance of the preoperative uptake of multiple brown tumor. PMID:9343725

  20. Markers of fibroblast-rich tumor stroma and perivascular cells in serous ovarian cancer: Inter- and intra-patient heterogeneity and impact on survival

    PubMed Central

    Corvigno, Sara; Wisman, G. Bea A.; Mezheyeuski, Artur; van der Zee, Ate G.J.; Nijman, Hans W.; Åvall-Lundqvist, Elisabeth; Östman, Arne; Dahlstrand, Hanna

    2016-01-01

    Inter- and intra-patient variations in tumor microenvironment of serous ovarian cancer are largely unexplored. We aimed to explore potential co-regulation of tumor stroma characteristics, analyze their concordance in primary and metastatic lesions, and study their impact on survival. A tissue microarray (TMA) with 186 tumors and 91 matched metastases was subjected to immunohistochemistry double staining with endothelial cell marker CD34 and fibroblast and pericyte markers α-SMA, PDGFβR and desmin. Images were digitally analyzed to yield “metrics” related to vasculature and stroma features. Intra-case analyses showed that PDGFβR in perivascular cells and fibroblasts were strongly correlated. Similar findings were observed concerning α-SMA. Most stroma characteristics showed large variations in intra-case comparisons of primary tumors and metastasis. Large PDGFβR-positive stroma fraction and high PDGFβFR positive perivascular intensity were both significantly associated with shorter survival in uni- and multi-variate analyses (HR 1.7, 95% CI 1.1-2.5; HR 1.7, 95% CI 1.1-2.8). In conclusion, we found PDGFβR- and α-SMA-expression to be largely independent of each other but concordantly activated in perivascular cells and in fibroblasts within the primary tumor. Stromal characteristics differed between primary tumors and metastases. PDGFβR in perivascular cells and in fibroblasts may be novel prognostic markers in serous ovarian cancer. PMID:26918345

  1. Expression of LATS family proteins in ovarian tumors and its significance.

    PubMed

    Xu, Bing; Sun, Duoxiang; Wang, Zhihua; Weng, Haiyan; Wu, Dabao; Zhang, Xuefen; Zhou, Ying; Hu, Weiping

    2015-06-01

    Epithelial ovarian cancer is composed of a diverse group of tumors that can be derived from the fallopian tube, endometrium, or ovary. In this study, we explored the expression levels of LATS family members in ovarian tumors using normal ovaries, fallopian tubes, and endometrium as controls. Immunohistochemistry studies of LATS1, LATS2, Pax8, and calretinin were performed on normal ovary, fallopian tube, normal endometrium, and ovarian tumor sections. Statistical analyses were conducted using the χ(2) test, Fisher exact test, or Kruskal-Wallis H test. Patient survival was analyzed using the Kaplan-Meier method. LATS1 was expressed in normal ovarian epithelia, endometrium, and fallopian tubes, whereas LATS2 expression was observed in the normal fallopian tubes and endometrium. High expressions of LATS1 and LATS2 in serous cystadenomas gradually decreased in borderline cystadenomas and carcinomas, respectively. However, an opposite expression pattern was observed in mucinous tumors. Low expressions of LATS1 and LATS2 were also detected in clear cell carcinoma. Both LATS1 and LATS2 expression levels significantly correlated with recurrence and stage; LATS1 levels were also related with tumor grades in serous carcinoma. However, univariate and multivariate Cox regression analyses revealed that high expression of LATS1 was associated with better prognosis in patients with serous carcinoma. Both LATS1 and LATS2 were not related with the clinical variables in mucinous and clear cell carcinoma. LATS1 expression levels might be a valuable survival indicator in ovarian serous carcinoma. PMID:25841306

  2. Ovarian Yolk Sac Tumor With High-Grade Serous Carcinoma in a 62-Year-Old Woman.

    PubMed

    McCarthy, Whitney A; Masand, Ramya P

    2016-06-01

    Ovarian yolk sac tumors are germ cell tumors that usually present in children and young women. Rarely, these tumors can arise in older women, usually in conjunction with surface epithelial tumors, suggesting divergent differentiation from the latter. The combination of mixed ovarian yolk sac tumor and high-grade serous carcinoma is rare, with only one case documented in the literature. We present a case of mixed ovarian yolk sac tumor and high-grade serous carcinoma in a postmenopausal woman, including a brief discussion of the immunohistochemical findings and differential diagnosis. Despite the rarity of mixed ovarian yolk sac tumor and surface epithelial tumors, it is important to recognize the biphasic nature of the tumor, which should prompt a thorough immunohistochemical evaluation. The therapeutic and prognostic implications of proper diagnosis cannot be overemphasized. PMID:26782153

  3. Metabolomic Changes Accompanying Transformation and Acquisition of Metastatic Potential in a Syngeneic Mouse Mammary Tumor Model*

    PubMed Central

    Lu, Xin; Bennet, Bryson; Mu, Euphemia; Rabinowitz, Joshua; Kang, Yibin

    2010-01-01

    Breast cancer is the most common cancer type for women in the western world. Despite decades of research, the molecular processes associated with breast cancer progression are still inadequately defined. Here, we focus on the systematic alteration of metabolism by using the state of the art metabolomic profiling techniques to investigate the changes of 157 metabolites during the progression of normal mouse mammary epithelial cells to an isogenic series of mammary tumor cell lines with increasing metastatic potentials. Our results suggest a two-step metabolic progression hypothesis during the acquisition of tumorigenic and metastatic abilities. Metabolite changes accompanying tumor progression are identified in the intracellular and secreted forms in several pathways, including glycolysis, the tricarboxylic acid cycle, the pentose phosphate pathway, fatty acid and nucleotide biosynthesis, and the GSH-dependent antioxidative pathway. These results suggest possible biomarkers of breast cancer progression as well as opportunities of interrupting tumor progression through the targeting of metabolic pathways. PMID:20139083

  4. AFP464 in Treating Patients With Metastatic or Refractory Solid Tumors That Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2014-02-21

    Male Breast Cancer; Recurrent Breast Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Primary Peritoneal Cavity Cancer; Recurrent Renal Cell Cancer; Stage IV Breast Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Primary Peritoneal Cavity Cancer; Stage IV Renal Cell Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  5. Non-classical HLA-class I expression in serous ovarian carcinoma: Correlation with the HLA-genotype, tumor infiltrating immune cells and prognosis

    PubMed Central

    Andersson, Emilia; Poschke, Isabel; Villabona, Lisa; Carlson, Joseph W; Lundqvist, Andreas; Kiessling, Rolf; Seliger, Barbara; Masucci, Giuseppe V

    2016-01-01

    In our previous studies, we have shown that patients with serous ovarian carcinoma in advanced surgical stage disease have a particularly poor prognosis if they carry the HLA-A*02 genotype. This represent a stronger prognostic factor than loss or downregulation of the MHC class I heavy chain (HC) on tumor cells. In this study, we investigated the expression of the non-classical, immune tolerogenic HLA -G and -E on the tumor cells along with the infiltration of immune cells in the tumor microenvironment. FFPE primary tumors from 72 patients with advanced stages of serous adenocarcinoma and metastatic cells present in ascites fluid from 8 additional patients were included in this study. Both expression of HLA-G and aberrant expression of HLA-E were correlated to a significant worse prognosis in patients with HLA-A*02, but not with different HLA genotypes. Focal cell expression of HLA-G correlated to a site-specific downregulation of classical MHC class I HC products and aberrant HLA-E expression, showing a poor survival. HLA-G was more frequently expressed in metastatic cells than in primary tumor lesions and the expression of HLA-G inversely correlated with the frequency of tumor infiltrating immune cells. All these parameters can contribute together to identify and discriminate subpopulations of patients with extremely poor prognosis and can give them the opportunity to receive, and benefit of individually tailored treatments. PMID:26942060

  6. Image-guided fine-needle aspiration cytology of ovarian tumors: An assessment of diagnostic efficacy

    PubMed Central

    Mehdi, Ghazala; Maheshwari, Veena; Afzal, Sheerin; Ansari, Hena A; Ansari, Maryem

    2010-01-01

    Background: Image-guided fine-needle aspiration cytology (FNAC) of ovarian lumps is being increasingly used for the successful diagnosis of ovarian tumors, although borderline cases may be difficult to diagnose by this method. Aim: To demonstrate the efficacy of image-guided FNAC in diagnosing ovarian tumors (benign and malignant) and to evaluate the usefulness of cytology as a mode of easy and rapid diagnosis of ovarian lumps. Materials and Methods: The study was conducted on 42 female patients. Clinical evaluation and relevant investigations were carried out. Diagnosis was established by FNAC performed under image guidance (ultrasonography/computed tomography). The cytological diagnosis was confirmed by histopathological examination. Results: Cytological diagnosis was rendered on all the 42 ovarian lesions, with a correct diagnosis in 34 cases, resulting in a diagnostic accuracy of 80.9%. Most of the cases with discordant diagnoses were surface epithelial tumors of low malignant potential and required histopathological examination for a final diagnosis. Conclusions: Image-guided FNAC is an inexpensive, rapid and fairly accurate procedure for the diagnosis of ovarian lesions. It provides a safe alternative to the more expensive, time consuming and cumbersome surgical route to diagnosis. PMID:21187883

  7. Inhibition of Ovarian Tumor Growth by Targeting the HU177 Cryptic Collagen Epitope.

    PubMed

    Caron, Jennifer M; Ames, Jacquelyn J; Contois, Liangru; Liebes, Leonard; Friesel, Robert; Muggia, Franco; Vary, Calvin P H; Oxburgh, Leif; Brooks, Peter C

    2016-06-01

    Evidence suggests that stromal cells play critical roles in tumor growth. Uncovering new mechanisms that control stromal cell behavior and their accumulation within tumors may lead to development of more effective treatments. We provide evidence that the HU177 cryptic collagen epitope is selectively generated within human ovarian carcinomas and this collagen epitope plays a role in SKOV-3 ovarian tumor growth in vivo. The ability of the HU177 epitope to regulate SKOV-3 tumor growth depends in part on its ability to modulate stromal cell behavior because targeting this epitope inhibited angiogenesis and, surprisingly, the accumulation of α-smooth muscle actin-expressing stromal cells. Integrin α10β1 can serve as a receptor for the HU177 epitope in α-smooth muscle actin-expressing stromal cells and subsequently regulates Erk-dependent migration. These findings are consistent with a mechanism by which the generation of the HU177 collagen epitope provides a previously unrecognized α10β1 ligand that selectively governs angiogenesis and the accumulation of stromal cells, which in turn secrete protumorigenic factors that contribute to ovarian tumor growth. Our findings provide a new mechanistic understanding into the roles by which the HU177 epitope regulates ovarian tumor growth and provide new insight into the clinical results from a phase 1 human clinical study of the monoclonal antibody D93/TRC093 in patients with advanced malignant tumors. PMID:27216148

  8. Signaling Circuits and Regulation of Immune Suppression by Ovarian Tumor-Associated Macrophages

    PubMed Central

    Cannon, Martin J.; Ghosh, Debopam; Gujja, Swetha

    2015-01-01

    The barriers presented by immune suppression in the ovarian tumor microenvironment present one of the biggest challenges to development of successful tumor vaccine strategies for prevention of disease recurrence and progression following primary surgery and chemotherapy. New insights gained over the last decade have revealed multiple mechanisms of immune regulation, with ovarian tumor-associated macrophages/DC likely to fulfill a central role in creating a highly immunosuppressive milieu that supports disease progression and blocks anti-tumor immunity. This review provides an appraisal of some of the key signaling pathways that may contribute to immune suppression in ovarian cancer, with a particular focus on the potential involvement of the c-KIT/PI3K/AKT, wnt/β-catenin, IL-6/STAT3 and AhR signaling pathways in regulation of indoleamine 2,3-dioxygenase expression in tumor-associated macrophages. Knowledge of intercellular and intracellular circuits that shape immune suppression may afford insights for development of adjuvant treatments that alleviate immunosuppression in the tumor microenvironment and enhance the clinical efficacy of ovarian tumor vaccines. PMID:26343197

  9. Protective effects of dendrosomal curcumin on an animal metastatic breast tumor.

    PubMed

    Farhangi, Baharak; Alizadeh, Ali Mohammad; Khodayari, Hamid; Khodayari, Saeed; Dehghan, Mohammad Javad; Khori, Vahid; Heidarzadeh, Alemeh; Khaniki, Mahmood; Sadeghiezadeh, Majid; Najafi, Farhood

    2015-07-01

    Curcumin has been shown to inhibit migration and invasion of cancer angiogenesis via interacting with key regulatory molecules like NF-κB. Rapidly metabolized and conjugated in the liver, curcumin has the limited systemic bioavailability. Previous results have shown a new light of potential biocompatibility, biodegradability, as well as anti-cancer effects of dendrosomal curcumin (DNC) in biological systems. The present study aims to deliberate the protective effects of DNC on metastatic breast tumor in vitro and in vivo. After the dosing procedure, twenty-seven female mice were divided into 40 and 80mg/kg groups of DNC, along with a control group to investigate the anti-metastatic effects of DNC on mammary tumor-bearing mice. In vitro results showed that the different concentrations of DNC reduced the migration and the adhesion of 4T1 cells after 24h (P<0.05). Under the dosing procedure, DNC was safe at 80mg/kg and lower doses. The treated DNC animals had a higher survival rate and lower metastatic signs (14%) compared to control (100%) (P<0.05). The metastatic tumors were more common in control mice than the treated groups in the lung, the liver and the sternum tissues. Animals treated with DNC had smaller tumor volume in comparison with control group (P<0.05). Final mean tumor volume reached to approximately 1.11, 0.31 and 0.27cm(3) in the control, and 40 and 80mg/kg DNC groups, respectively (P<0.05). Furthermore, suppression of NF-κB expression by DNC led to down-regulation of VEGF, COX-2, and MMP-9 expressions in the breast tumor, the lung, the brain, the spleen and the liver tissues (P<0.05). These outcomes indicate that dendrosomal curcumin has a chemoprotective effect on the breast cancer metastasis through suppression of NF-κB and its regulated gene products. PMID:25863259

  10. Selective photothermal laser-tissue interaction with augmentation of immunoadjuvants in treatment of DMBA-4 metastatic mammary tumors in rats

    NASA Astrophysics Data System (ADS)

    Chen, Wei R.; Liu, Hong; Wolf, Roman F.; Lucroy, Michael D.; Nordquist, Robert E.

    2002-09-01

    Induced anti-tumor immunity can be the most effective and long-term cure for cancers, particularly for metastatic tumors. Laser immunotherapy has been developed to induce such immunological responses in rats bearing DMBA-4 metastatic mammary tumors. It involves an intratumoral administration of a laser-absorbing dye (indocyanine green) and a specially formulated immunoadjuvant (glycated chitosan), followed by an irradiation of a near-infrared laser (805-nm diode laser). To understand the immunity induced in this tumor model, immunization using freeze-thaw cell lysates against the DMBA-4 tumors was performed, followed by the tumor challenge twenty-one days later. Also performed is the surgical removal of the primary tumors of the rats before the observation of metastatic tumors. The immunization only delayed the emergence of the primary and metastases in the rats but did not provide immunity against the tumor challenge. After surgical removal of the primary tumors, the tumors re-emerged at the primary sites and the metastases developed at multiple remote sites. In contrast, laser immunotherapy cured rats experienced tumor regression and eradication. Our research has provided strong support for the working mechanism of laser immunotherapy. The experimental results showed that selective photothermal laser-tissue interaction with a complementary use of immunoadjuvant could be a potential therapy for treatment of metastatic tumors by inducing a tumor-specific, long-lasting immunity.

  11. Interstitial laser immunotherapy for treatment of metastatic mammary tumors in rats

    NASA Astrophysics Data System (ADS)

    Figueroa, Daniel; Joshi, Chet; Wolf, Roman F.; Walla, Jonny; Goddard, Jessica; Martin, Mallory; Kosanke, Stanley D.; Broach, Fred S.; Pontius, Sean; Brown, Destiny; Li, Xiaosong; Howard, Eric; Nordquist, Robert E.; Hode, Tomas; Chen, Wei R.

    2011-03-01

    Thermal therapy has been used for cancer treatment for more than a century. While thermal effect can be direct, immediate, and controllable, it is not sufficient to completely eradicate tumors, particularly when tumors have metastasized locally or to the distant sites. Metastases are the major cause of treatment failure and cancer deaths. Current available therapies, such as surgery, radiation, and chemotherapy, only have limited curative effects in patients with late-stage, metastatic cancers. Immunotherapy has been considered as the ultimate approach for cancer treatment since a systemic, anti-tumor, immunological response can be induced. Using the combination of photothermal therapy and immunotherapy, laser immunotherapy (LIT),a novel immunotherapy modality for late-stage cancer treatment, has been developed. LIT has shown great promise in pre-clinical studies and clinical breast cancer and melanoma pilot trials. However, the skin color and the depth of the tumor have been challenges for effective treatment with LIT. To induce a thermal destruction zone of appropriate size without causing thermal damage on the skin, we have developed interstitial laser immunotherapy (ILIT) using a cylindrical diffuser. To determine the effectiveness of ILIT, we treated the DMBA-4 metastatic tumors in rats. The thermal damage in tumor tissue was studied using TTC immersion and hematoxolin and eosin (H & E) staining. Also observed was the overall survival of the treated animals. Our results demonstrated that the ILIT could impact a much larger tumor area, and it significantly reduced the surface damage compared with the early version of non-invasive LIT. The survival data also indicate that ILIT has the potential to become an effective tool for the treatment of deeper, larger, and metastatic tumors, with reduced side effects.

  12. A case-control study of borderline ovarian tumors: the influence of perineal exposure to talc.

    PubMed

    Harlow, B L; Weiss, N S

    1989-08-01

    The authors interviewed 116 female residents of western Washington State with serous and mucinous borderline ovarian tumors diagnosed between 1980 and 1985 and questioned them on their use of hygienic powders. A sample of 158 control women from the same counties were identified through random digit dialing and were interviewed as well. Neither the perineal application of baby powder nor the perineal application of cornstarch was associated with an appreciably altered risk of borderline ovarian tumors. However, women who used deodorizing powders alone or in combination with other talc-containing powders had 2.8 times the risk (95% confidence interval 1.1-11.7) of women who had not had perineal exposure to powder. These results suggest that future studies of ovarian tumors in relation to the application of talc-containing powders should consider ascertaining the specific type(s) of powder used. PMID:2750733

  13. Impact of FOXL2 mutations on signaling in ovarian granulosa cell tumors.

    PubMed

    Leung, Dilys T H; Fuller, Peter J; Chu, Simon

    2016-03-01

    Granulosa cell tumors (GCT) are unique sex-cord stromal tumors which account for ∼8% of all ovarian malignancies. They exhibit morphological, biochemical and hormonal features similar to proliferating granulosa cells of the preovulatory follicle, including estrogen and inhibin synthesis. A somatic missense mutation in the forkhead box L2 (FOXL2) gene (C134W) is unique to adult GCT, and absent in other ovarian cancers. FOXL2 is a transcription factor that plays a critical role in ovarian function, in particular, proliferation and differentiation of granulosa cells. The molecular mechanisms underlying the pathogenicity of the mutant FOXL2 remain unresolved. Here we review the molecular alterations known to be associated with mutant FOXL2 and the potential signaling implications. Several studies suggest that dysregulated FOXL2 function may alter cell cycle progression and apoptosis. Further insights into the molecular mechanism of GCT pathophysiology may identify therapeutic targets for the treatment of these tumors. PMID:26791928

  14. Ablation techniques for primary and metastatic liver tumors.

    PubMed

    Ryan, Michael J; Willatt, Jonathon; Majdalany, Bill S; Kielar, Ania Z; Chong, Suzanne; Ruma, Julie A; Pandya, Amit

    2016-01-28

    Ablative treatment methods have emerged as safe and effective therapies for patients with primary and secondary liver tumors who are not surgical candidates at the time of diagnosis. This article reviews the current literature and describes the techniques, complications and results for radiofrequency ablation, microwave ablation, cryoablation, and irreversible electroporation. PMID:26839642

  15. Ablation techniques for primary and metastatic liver tumors

    PubMed Central

    Ryan, Michael J; Willatt, Jonathon; Majdalany, Bill S; Kielar, Ania Z; Chong, Suzanne; Ruma, Julie A; Pandya, Amit

    2016-01-01

    Ablative treatment methods have emerged as safe and effective therapies for patients with primary and secondary liver tumors who are not surgical candidates at the time of diagnosis. This article reviews the current literature and describes the techniques, complications and results for radiofrequency ablation, microwave ablation, cryoablation, and irreversible electroporation. PMID:26839642

  16. Identification of Genes Associated with Local Aggressiveness and Metastatic Behavior in Soft Tissue Tumors12

    PubMed Central

    Cunha, Isabela Werneck; Carvalho, Katia Candido; Martins, Waleska Keller; Marques, Sarah Martins; Muto, Nair Hideko; Falzoni, Roberto; Rocha, Rafael Malagoli; Aguiar, Samuel; Simoes, Ana C. Q.; Fahham, Lucas; Neves, Eduardo Jordão; Soares, Fernando Augusto; Reis, Luiz Fernando Lima

    2010-01-01

    Soft tissue tumors represent a group of neoplasia with different histologic and biological presentations varying from benign, locally confined to very aggressive and metastatic tumors. The molecular mechanisms responsible for such differences are still unknown. The understanding of these molecular alterations mechanism will be critical to discriminate patients who need systemic treatment from those that can be treated only locally and could also guide the development of new drugs' against this tumors. Using 102 tumor samples representing a large spectrum of these tumors, we performed expression profiling and defined differentially expression genes that are likely to be involved in tumors that are locally aggressive and in tumors with metastatic potential. We described a set of 12 genes (SNRPD3, MEGF9, SPTAN-1, AFAP1L2, ENDOD1, SERPIN5, ZWINTAS, TOP2A, UBE2C, ABCF1, MCM2, and ARL6IP5) showing opposite expression when these two conditions were compared. These genes are mainly related to cell-cell and cell-extracellular matrix interactions and cell proliferation and might represent helpful tools for a more precise classification and diagnosis as well as potential drug targets. PMID:20165692

  17. Peritoneal tumor spread in serous ovarian cancer-epithelial mesenchymal status and outcome

    PubMed Central

    Auer, Katharina; Bachmayr-Heyda, Anna; Aust, Stefanie; Sukhbaatar, Nyamdelger; Reiner, Agnes Teresa; Grimm, Christoph; Horvat, Reinhard; Zeillinger, Robert; Pils, Dietmar

    2015-01-01

    In this study we aimed to analyze the biological mechanisms underlying apparently different modes of peritoneal tumor spread in serous ovarian cancer: miliary (widespread, millet-like lesions) versus non-miliary (bigger, exophytically growing implants). Tumor tissues and ascites from 23 chemotherapy naive patients were analyzed by RNA-sequencing and flow cytometry. On the basis of differential gene expression between miliary and non-miliary, gene signatures were developed. A calculated tumor spread factor revealed a significant independent negative impact of miliary spread on overall survival (HR 3.77; CI95 1.14–12.39; p = 0.029) in an independent cohort of 165 serous ovarian cancer patients. Comparing previously published epithelial-mesenchymal transition (EMT) gene signatures, non-miliary spread correlated significantly with a reduced epithelial status. We conclude that serous ovarian cancer is a heterogeneous disease with distinct modes of peritoneal tumor spread, differing not only in clinical appearance, but also in molecular characteristics and outcome.. EMT, peritoneal inflammation status, and therapeutic options are discussed. Significance More than half of serous epithelial ovarian cancer patients present with a newly described type of intraperitoneal tumor spread, associated with differences in the inflammation status, activated oncogenic pathways, lack of EMT, and thus reduced overall survival. Both, the diminished immune reaction and the enhanced epithelial and malignant characteristics of the tumor cells open new avenues for therapeutic options and strategies, like Catumaxomab, already in clinical use. PMID:25991672

  18. Non-lethal heat treatment of cells results in reduction of tumor initiation and metastatic potential

    SciTech Connect

    Kim, Yoo-Shin; Lee, Tae Hoon; O'Neill, Brian E.

    2015-08-14

    Non-lethal hyperthermia is used clinically as adjuvant treatment to radiation, with mixed results. Denaturation of protein during hyperthermia treatment is expected to synergize with radiation damage to cause cell cycle arrest and apoptosis. Alternatively, hyperthermia is known to cause tissue level changes in blood flow, increasing the oxygenation and radiosensitivity of often hypoxic tumors. In this study, we elucidate a third possibility, that hyperthermia alters cellular adhesion and mechanotransduction, with particular impact on the cancer stem cell population. We demonstrate that cell heating results in a robust but temporary loss of cancer cell aggressiveness and metastatic potential in mouse models. In vitro, this heating results in a temporary loss in cell mobility, adhesion, and proliferation. Our hypothesis is that the loss of cellular adhesion results in suppression of cancer stem cells and loss of tumor virulence and metastatic potential. Our study suggests that the metastatic potential of cancer is particularly reduced by the effects of heat on cellular adhesion and mechanotransduction. If true, this could help explain both the successes and failures of clinical hyperthermia, and suggest ways to target treatments to those who would most benefit. - Highlights: • Non-lethal hyperthermia treatment of cancer cells is shown to cause a reduction in rates of tumor initiation and metastasis. • Dynamic imaging of cells during heat treatment shows temporary changes in cell shape, cell migration, and cell proliferation. • Loss of adhesion may lead to the observed effect, which may disproportionately impact the tumor initiating cell fraction. • Loss or suppression of the tumor initiating cell fraction results in the observed loss of metastatic potential in vivo. • This result may lead to new approaches to synergizing hyperthermia with surgery, radiation, and chemotherapy.

  19. Mesotheliomas show higher hyaluronan positivity around tumor cells than metastatic pulmonary adenocarcinomas.

    PubMed

    Törrönen, Kari; Soini, Ylermi; Pääkkö, Paavo; Parkkinen, Jyrki; Sironen, Reijo; Rilla, Kirsi

    2016-10-01

    Hyaluronan is a unique glycosaminoglycan of the extracellular matrix, abundant in normal connective tissues but highly increased in many pathological conditions like cancer. Mesothelioma, one of the most malignant cancer types, is associated with high content of hyaluronan, with elevated levels of hyaluronan in pleural effusions and serum of the patients. Metastatic lung adenocarcinomas are typically less aggressive and have a better prognosis as compared to mesotheliomas, a reason why it is highly important to find reliable tools to differentiate these cancer types. The main purpose of this study was to evaluate the amount of hyaluronan, hyaluronan producing synthases (HAS's) and hyaluronan receptor CD44, in mesothelioma and metastatic lung adenocarcinomas. Furthermore, we wanted to clarify the role of hyaluronan, CD44 and HAS's as putative markers for differentiating malignant mesothelioma from metastatic lung adenocarcinomas. The main finding of this study was that mesotheliomas are significantly more positive for hyaluronan staining than metastatic adenocarcinomas. Unexceptionally, a trend of CD44 positivity of stromal cells was higher in adenocarcinomas as compared to mesotheliomas. However, no statistically significant differences were found between the staining of any of the HAS isoenzymes either in tumor cells or stromal cells of different groups of cases. The results show that there are significant differences in hyaluronan content between metastatic lung adenocarcinomas and mesotheliomas. However, as previous studies have suggested, hyaluronan alone is not a sufficient independent marker for diagnostic differentiation of these cancer types, but could be utilized as a combination together with other specific markers. PMID:26912058

  20. Uterine tumor resembling ovarian sex cord tumor. Case report and review of literature.

    PubMed

    Stefanovic, A; Jeremic, K; Kadija, S; Mitrovic, M; Filimonovic, D; Jankovic-Raznatovic, S; Tavcar, J

    2013-01-01

    A uterine tumor resembling an ovarian sex cord tumor (UTROSCT) shows a poly phenotypic immunophenotype with coexpression of epithelial, myoid, and sex cord markers, as well as hormone receptors. The authors present a case of a 59-year-old multiparous woman admitted to the Institute of Gynecology and Obstetrics Clinical Centre of Serbia in January 2010 due to prolonged vaginal bleeding and abdominal discomfort. The vaginal ultrasound showed an enlarged uterus size of 100 x 74 x 81 mm, with extended cavity with an unhomogenic content and myomas sized 54 x 69 mm located in fundus with secondary changes. She underwent abdominal hysterectomy with adnexectomy. Microscopic examination revealed submucosal uterine tumor with variabile histological organization that had anastomotic trabeculae with solid cellular grupations. Rare mitotic figures (2/10 HPF) were found. Additional imunohistochemistry showed immunophenotype: the sex cord areas were positive for vimentin(++), aSMA(++), AE1/AE3(+), PR(+), and ER(+). The poly phenotypic immunophenotype can be useful in differential diagnosis from other neoplasms but also suggests an origin of UTROSCT from uncommitted stem cell enabling for multidirectional differentiation. PMID:23967565

  1. Uterine Tumor Resembling Ovarian Sex Cord Tumor (UTROSCT) Commonly Exhibits Positivity With Sex Cord Markers FOXL2 and SF-1 but Lacks FOXL2 and DICER1 Mutations.

    PubMed

    Croce, Sabrina; de Kock, Leanne; Boshari, Talia; Hostein, Isabelle; Velasco, Valerie; Foulkes, William D; McCluggage, W Glenn

    2016-07-01

    Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare neoplasm which morphologically and immunohistochemically exhibits overlap with an ovarian sex cord tumor. Although many of these neoplasms are positive with markers of ovarian sex cord-stromal tumors, staining is often limited and the pathogenesis of UTROSCT is unknown. To further explore the sex cord lineage of UTROSCT, we studied 19 of these neoplasms and examined the expression of 2 recently described markers of ovarian sex cord-stromal tumors, FOXL2, and steroidogenic factor-1. We also undertook FOXL2 and DICER1 mutation analysis in these cases; a somatic missense mutation in codon C134W (402C→G) of FOXL2 gene has been demonstrated in the vast majority (>95%) of ovarian adult granulosa cell tumors and somatic DICER1 mutations are found in approximately 60% of ovarian Sertoli-Leydig cell tumors. Ten of 19 cases (53%) exhibited nuclear immunoreactivity with FOXL2 and 11 of 19 (58%) exhibited nuclear staining with steroidogenic factor-1. Neither FOXL2 nor DICER1 mutations were identified in any case where there was sufficient tumor tissue for analysis (18 and 9 cases, respectively). Despite exhibiting an immunophenotype characteristic of a sex cord-stromal tumor, mutations in FOXL2 and DICER1, the 2 most common mutations hitherto reported in ovarian sex cord-stromal tumors, are not a feature of UTROSCT. PMID:26598979

  2. Cancer Associated Fibroblasts express pro-inflammatory factors in human breast and ovarian tumors

    SciTech Connect

    Erez, Neta; Glanz, Sarah; Raz, Yael; Avivi, Camilla; Barshack, Iris

    2013-08-02

    Highlights: •CAFs in human breast and ovarian tumors express pro-inflammatory factors. •Expression of pro-inflammatory factors correlates with tumor invasiveness. •Expression of pro-inflammatory factors is associated with NF-κb activation in CAFs. -- Abstract: Inflammation has been established in recent years as a hallmark of cancer. Cancer Associated Fibroblasts (CAFs) support tumorigenesis by stimulating angiogenesis, cancer cell proliferation and invasion. We previously demonstrated that CAFs also mediate tumor-enhancing inflammation in a mouse model of skin carcinoma. Breast and ovarian carcinomas are amongst the leading causes of cancer-related mortality in women and cancer-related inflammation is linked with both these tumor types. However, the role of CAFs in mediating inflammation in these malignancies remains obscure. Here we show that CAFs in human breast and ovarian tumors express high levels of the pro-inflammatory factors IL-6, COX-2 and CXCL1, previously identified to be part of a CAF pro-inflammatory gene signature. Moreover, we show that both pro-inflammatory signaling by CAFs and leukocyte infiltration of tumors are enhanced in invasive ductal carcinoma as compared with ductal carcinoma in situ. The pro-inflammatory genes expressed by CAFs are known NF-κB targets and we show that NF-κB is up-regulated in breast and ovarian CAFs. Our data imply that CAFs mediate tumor-promoting inflammation in human breast and ovarian tumors and thus may be an attractive target for stromal-directed therapeutics.

  3. Ribosomal S6 kinase 4 (RSK4) expression in ovarian tumors and its regulation by antineoplastic drugs in ovarian cancer cell lines.

    PubMed

    Arechavaleta-Velasco, Fabian; Zeferino-Toquero, Moises; Estrada-Moscoso, Isaias; Imani-Razavi, Fazlollah Shahram; Olivares, Aleida; Perez-Juarez, Carlos Eduardo; Diaz-Cueto, Laura

    2016-02-01

    Survival rate in ovarian cancer depends on the stage of the disease. RSK4, which has been considered as a tumor suppressor factor, controls cells invasion due to its antiinvasive and antimetastatic properties. Modulation of RSK4 expression could be an important event to increase the survival rate in ovarian cancer patients. Thus, the goal of the present study was to establish the differences in RSK4 expression among normal, benign and malignant ovarian tissues and to determine whether antineoplastic drugs regulate its expression in SKOV3 and TOV-112D cells. RSK4 levels in 30 malignant ovarian tumors, 64 benign tumors and 36 normal ovary tissues were determined by reverse transcription polymerase chain reaction and Western blot. Modulation of RSK4 expression by two antineoplastic drugs (cisplatin and vorinostat) was also studied in the SKOV3 and TOV-112D ovarian cancer cell lines using the same techniques. RSK4 mRNA and protein levels were decreased in malignant ovarian tumors as compared to benign tumors and normal tissue. These low-RSK4 levels were significantly associated with advanced stages of ovarian cancer. RSK4 expression was increased after incubation of SKOV3 and TOV-112D cell lines with cisplatin and vorinostat for 24 h. The combination of these antineoplastic drugs did not produce a synergistic or additive effect. These results suggest that RSK4 is expressed at low levels in malignant ovarian tumors, which correlates with advanced stages of the disease. Additionally, RSK4 expression is regulated by cisplatin and vorinostat in two ovarian cancer cell lines. PMID:26732474

  4. Cisplatin Resistant Spheroids Model Clinically Relevant Survival Mechanisms in Ovarian Tumors.

    PubMed

    Chowanadisai, Winyoo; Messerli, Shanta M; Miller, Daniel H; Medina, Jamie E; Hamilton, Joshua W; Messerli, Mark A; Brodsky, Alexander S

    2016-01-01

    The majority of ovarian tumors eventually recur in a drug resistant form. Using cisplatin sensitive and resistant cell lines assembled into 3D spheroids we profiled gene expression and identified candidate mechanisms and biological pathways associated with cisplatin resistance. OVCAR-8 human ovarian carcinoma cells were exposed to sub-lethal concentrations of cisplatin to create a matched cisplatin-resistant cell line, OVCAR-8R. Genome-wide gene expression profiling of sensitive and resistant ovarian cancer spheroids identified 3,331 significantly differentially expressed probesets coding for 3,139 distinct protein-coding genes (Fc >2, FDR < 0.05) (S2 Table). Despite significant expression changes in some transporters including MDR1, cisplatin resistance was not associated with differences in intracellular cisplatin concentration. Cisplatin resistant cells were significantly enriched for a mesenchymal gene expression signature. OVCAR-8R resistance derived gene sets were significantly more biased to patients with shorter survival. From the most differentially expressed genes, we derived a 17-gene expression signature that identifies ovarian cancer patients with shorter overall survival in three independent datasets. We propose that the use of cisplatin resistant cell lines in 3D spheroid models is a viable approach to gain insight into resistance mechanisms relevant to ovarian tumors in patients. Our data support the emerging concept that ovarian cancers can acquire drug resistance through an epithelial-to-mesenchymal transition. PMID:26986722

  5. Cisplatin Resistant Spheroids Model Clinically Relevant Survival Mechanisms in Ovarian Tumors

    PubMed Central

    Miller, Daniel H.; Medina, Jamie E.; Hamilton, Joshua W.; Messerli, Mark A.; Brodsky, Alexander S.

    2016-01-01

    The majority of ovarian tumors eventually recur in a drug resistant form. Using cisplatin sensitive and resistant cell lines assembled into 3D spheroids we profiled gene expression and identified candidate mechanisms and biological pathways associated with cisplatin resistance. OVCAR-8 human ovarian carcinoma cells were exposed to sub-lethal concentrations of cisplatin to create a matched cisplatin-resistant cell line, OVCAR-8R. Genome-wide gene expression profiling of sensitive and resistant ovarian cancer spheroids identified 3,331 significantly differentially expressed probesets coding for 3,139 distinct protein-coding genes (Fc >2, FDR < 0.05) (S2 Table). Despite significant expression changes in some transporters including MDR1, cisplatin resistance was not associated with differences in intracellular cisplatin concentration. Cisplatin resistant cells were significantly enriched for a mesenchymal gene expression signature. OVCAR-8R resistance derived gene sets were significantly more biased to patients with shorter survival. From the most differentially expressed genes, we derived a 17-gene expression signature that identifies ovarian cancer patients with shorter overall survival in three independent datasets. We propose that the use of cisplatin resistant cell lines in 3D spheroid models is a viable approach to gain insight into resistance mechanisms relevant to ovarian tumors in patients. Our data support the emerging concept that ovarian cancers can acquire drug resistance through an epithelial-to-mesenchymal transition. PMID:26986722

  6. Gene expression profiling of single circulating tumor cells in ovarian cancer - Establishment of a multi-marker gene panel.

    PubMed

    Blassl, Christina; Kuhlmann, Jan Dominik; Webers, Alessandra; Wimberger, Pauline; Fehm, Tanja; Neubauer, Hans

    2016-08-01

    The presence of circulating tumor cells (CTCs) in the blood of ovarian cancer patients was shown to correlate with decreased overall survival, whereby CTCs with epithelial-mesenchymal-transition (EMT) or stem-like traits are supposed to be involved in metastatic progression and recurrence. Thus, investigating the transcriptional profiles of CTCs might help to identify therapy resistant tumor cells and to overcome treatment failure. For this purpose, we established a multi-marker panel for the molecular characterization of single CTCs, detecting epithelial (EpCAM, Muc-1, CK5/7), EMT (N-cadherin, Vimentin, Snai1/2, CD117, CD146, CD49f) and stem cell (CD44, ALDH1A1, Nanog, SOX2, Notch1/4, Oct4, Lin28) associated transcripts. First primer specificity and PCR-performance of the multiplex-RT-PCRs were successfully validated on genomic DNA and cDNA isolated from OvCar3 cells. The assay sensitivity of the epithelial panel was evaluated by adding defined numbers of tumor cells into the blood of healthy donors and performing a subsequent immunomagnetic tumor cell enrichment (AdnaTest OvarianCancerSelect), resulting in a 100% concordance for the epithelial markers EpCAM and Muc-1 to the AdnaTest OvarianCancerDetect. Additionally, by processing blood from ovarian cancer patients, high assay sensitivity could be verified. In blood of healthy donors no signals for epithelial markers were detected, for EMT and stem cell markers, however, signals were obtained mainly originating from leukocytes which calls for single cell analysis. To that aim by using the ovarian cancer cell line OvCar3, we successfully established a workflow enabling the characterization of single CTCs. It consists of a density gradient-dependent enrichment for nucleated cells, a depletion of CD45-positive cells of hematopoietic origin followed by immunofluorescent labeling of CTCs by EpCAM and Muc-1. Single CTCs are then isolated by micromanipulation and processed for panel gene expression profiling. Finally

  7. Characterization of the MDSC proteome associated with metastatic murine mammary tumors using label-free mass spectrometry and shotgun proteomics.

    PubMed

    Boutté, Angela M; McDonald, W Hayes; Shyr, Yu; Yang, Li; Lin, P Charles

    2011-01-01

    Expansion of Gr-1+/CD11b+ myeloid derived suppressor cells (MDSCs) is governed by the presence of increasingly metastatic, malignant primary tumors. Metastasis, not the primary tumor, is often the cause of mortality. This study sought to fully characterize the MDSC proteome in response to metastatic and non-metastatic mammary tumors using label-free mass spectrometry shotgun proteomics in a mouse model with tumor cell lines, 67NR and 4T1, derived from the same tumor. 67NR cells form only primary mammary tumors, whereas 4T1 cells readily metastasize to the lungs, lymph nodes, and blood. Overall analysis identified a total of 2825 protein groups with a 0.78% false discovery rate. Of the 2814 true identifications, 43 proteins were exclusive to the 67NR group, 153 were exclusive to the 4T1 group, and 2618 were shared. Among the shared cohort, 26 proteins were increased and 31 were decreased in the metastatic 4T1 cohort compared to non-metastatic 67NR controls after filtering. MDSCs selectively express proteins involved in the γ-glutamyl transferase, glutathione synthase pathways, CREB transcription factor signaling, and other pathways involved in platelet aggregation, as well as lipid and amino acid metabolism, in response to highly metastatic 4T1 tumors. Cell cycle regulation dominated protein pathways and ontological groups of the 67NR non-metastatic group. Not only does this study provide a starting point to identify potential biomarkers of metastasis expressed by MDSCs; it identifies critical pathways that are unique to non-metastatic and metastatic conditions. Therapeutic interventions aimed at these pathways in MDSC may offer a new route to control malignancy and metastasis. PMID:21853032

  8. Cutaneous metastatic adenocarcinoma complicated by spontaneous tumor lysis syndrome: A case report

    PubMed Central

    WANG, YU; YUAN, CAIJUN; LIU, XIAOMEI

    2014-01-01

    The present study reports the case of a 71-year-old female with metastatic adenocarcinoma of the skin who developed tumor lysis syndrome (TLS) upon admittance to the First Affiliated Hospital of Liaoning Medical University (Jinzhou, China). The patient presented to the hospital due to multiple subcutaneous nodules, lethargy and weakness, but succumbed without any cancer therapy. Metastases to the skin from solid carcinomas are uncommon, and several studies have reported patients with minimal primary symptoms despite extensive metastatic skin disease. However, few cases were accompanied with spontaneous TLS at the time of presentation. TLS may be a severe complication during the therapy for hematological and oncological diseases. Although spontaneous TLS in internal tumors has been reported, it is extremely rare. The present study highlights the fact that multiple subcutaneous metastases may occur with the symptoms of spontaneous TLS, and may be key for the early recognition of this syndrome. PMID:25013514

  9. Nav1.5 regulates breast tumor growth and metastatic dissemination in vivo

    PubMed Central

    Nelson, Michaela; Yang, Ming; Millican-Slater, Rebecca; Brackenbury, William J.

    2015-01-01

    Voltage-gated Na+ channels (VGSCs) mediate action potential firing and regulate adhesion and migration in excitable cells. VGSCs are also expressed in cancer cells. In metastatic breast cancer (BCa) cells, the Nav1.5 α subunit potentiates migration and invasion. In addition, the VGSC-inhibiting antiepileptic drug phenytoin inhibits tumor growth and metastasis. However, the functional activity of Nav1.5 and its specific contribution to tumor progression in vivo has not been delineated. Here, we found that Nav1.5 is up-regulated at the protein level in BCa compared with matched normal breast tissue. Na+ current, reversibly blocked by tetrodotoxin, was retained in cancer cells in tumor tissue slices, thus directly confirming functional VGSC activity in vivo. Stable down-regulation of Nav1.5 expression significantly reduced tumor growth, local invasion into surrounding tissue, and metastasis to liver, lungs and spleen in an orthotopic BCa model. Nav1.5 down-regulation had no effect on cell proliferation or angiogenesis within the in tumors, but increased apoptosis. In vitro, Nav1.5 down-regulation altered cell morphology and reduced CD44 expression, suggesting that VGSC activity may regulate cellular invasion via the CD44-src-cortactin signaling axis. We conclude that Nav1.5 is functionally active in cancer cells in breast tumors, enhancing growth and metastatic dissemination. These findings support the notion that compounds targeting Nav1.5 may be useful for reducing metastasis. PMID:26452220

  10. The preclinical therapeutic response of residual metastatic disease is distinct from its primary tumor of origin

    PubMed Central

    Day, Chi-Ping; Carter, John; Bonomi, Carrie; Hollingshead, Melinda; Merlino, Glenn

    2011-01-01

    Cancer-related deaths are caused principally by recurrence and metastasis arising from residual disease, whose therapeutic responses has been suggested to be substantially different from primary tumors. However, experimental animal models designed for evaluating the therapeutic responses of residual disease are mostly lacking. To overcome this deficiency, we have developed a preclinical model that recapitulates the progression for advanced non-small cell lung cancer (NSCLC). An archived Lewis Lung Carcinoma mouse tumor, propagated only through serial in vivo transplantation and never adapted to cell culture, was stably labeled using lentivirus-encoded biomarkers, consistently expressed through an RNA polymerase II promoter. Labeled tumors were inoculated into syngeneic immunocompetent mice to ensure superior tumor-host interactions. Primary tumors were resected upon reaching a predetermined size, following by treatment in a setting akin to post-surgical first-line adjuvant chemotherapy and routine imaging to monitor the progression of pulmonary metastasis. We discovered that efficacious treatment, instead of reducing disease growth rates, significantly prolonged disease-free survival (DFS) and overall survival (OS). As in the clinic, cisplatin-based regimes were more effective in this model. However, the response of metastases to specific agents could not be predicted from, and often opposed, their effects on subcutaneous “primary” tumors, possibly due to their distinct growth kinetics and host interactions. We here introduce a clinically relevant model of residual metastatic disease that may more accurately predict the therapeutic response of recurrent, metastatic disease. PMID:21312195

  11. Tracking sub-clonal TP53 mutated tumor cells in human metastatic renal cell carcinoma

    PubMed Central

    Bousquet, Guilhem; Bouchtaoui, Morad El; Leboeuf, Christophe; Battistella, Maxime; Varna, Mariana; Ferreira, Irmine; Plassa, Louis-François; Hamdan, Diaddin; Bertheau, Philippe; Feugeas, Jean-Paul; Damotte, Diane; Janin, Anne

    2015-01-01

    Renal Cell Carcinomas (RCCs) are heterogeneous tumors with late acquisition of TP53 abnormalities during their evolution. They harbor TP53 abnormalities in their metastases. We aimed to study TP53 gene alterations in tissue samples from primary and metastatic RCCs in 36 patients followed up over a median of 4.2 years, and in xenografted issued from primary RCCs. In 36 primary RCCs systematically xenografted in mice, and in biopsies of metastases performed whenever possible during patient follow-up, we studied p53-expressing tumor cells and TP53 gene abnormalities. We identified TP53 gene alterations in primary tumors, metastases and xenografts. Quantification of tumors cells with TP53 gene alterations showed a significant increase in the metastases compared to the primary RCCs, and, strikingly, the xenografts were similar to the metastases and not to the primary RCCs from which they were derived. Using laser-microdissection of p53-expressing tumor cells, we identified TP53-mutated tumor cells in the xenografts derived from the primary RCC, and in a lung metastasis later developed in one patient. The mutation enabled us to track back their origin to a minority sub-clone in the primary heterogeneous RCC. Combining in situ and molecular analyses, we demonstrated a clonal expansion in a living patient with metastatic RCC. PMID:26002555

  12. Function of immunoadjuvants in laser immunotherapy for treatment of metastatic breast tumors in rats

    NASA Astrophysics Data System (ADS)

    Chen, Wei R.; Liu, Hong; Wolf, Roman F.; Lucroy, Michael D.; Nordquist, Robert E.

    2002-06-01

    Tumor cell destruction usually induces host immune responses, such as local inflammation and increased activities of macrophages and neutrophils. Use of immunoadjuvant can usually enhance such immune activities. Laser immunotherapy is designed to use the combination of laser photothermal and immunological interactions to induce long-term antitumor immunity with the help of immunoadjuvant. It uses a selective hyperthermia for acute tumor destruction through an intratumor administration of indocyanine green and a noninvasive irradiation by an 805-nm laser. The concurrent in situ administration of immunoadjuvant helped achieve the desired effect: tumor eradication and antitumor immunity. The current study further explores the function of immunoadjuvants in laser immunotherapy by testing four different adjuvants: glycated chitosan, complete Freund's adjuvant, incomplete Freund's adjuvant, and c-parvum. Each adjuvant provided long-term tumor cure in the treatment of a metastatic mammary tumor model in rats. However, glycated chitosan and complete Freund's adjuvant were most effective with 25% and 18% long- term cure rates, respectively. Different concentrations of glycated chitosan were also used in treatment of rats bearing metastatic breast tumors.

  13. Selection of Mesenchymal-Like Metastatic Cells in Primary Tumors – An in silico Investigation

    PubMed Central

    Narang, Vipin; Wong, Shek Yoon; Leong, Shiang Rong; Harish, Bindu; Abastado, Jean-Pierre; Gouaillard, Alexandre

    2012-01-01

    In order to metastasize, cancer cells must undergo phenotypic transition from an anchorage-dependent form to a motile form via a process referred to as epithelial to mesenchymal transition. It is currently unclear whether metastatic cells emerge late during tumor progression by successive accumulation of mutations, or whether they derive from distinct cell populations already present during the early stages of tumorigenesis. Similarly, the selective pressures that drive metastasis are poorly understood. Selection of cancer cells with increased proliferative capacity and enhanced survival characteristics may explain how some transformations promote a metastatic phenotype. However, it is difficult to explain how cancer cells that disseminate can emerge due to such selective pressure, since these cells usually remain dormant for prolonged periods of time. In the current study, we have used in silico modeling and simulation to investigate the hypothesis that mesenchymal-like cancer cells evolve during the early stages of primary tumor development, and that these cells exhibit survival and proliferative advantages within the tumor microenvironment. In an agent-based tumor microenvironment model, cancer cell agents with distinct sets of attributes governing nutrient consumption, proliferation, apoptosis, random motility, and cell adhesion were allowed to compete for space and nutrients. These simulation data indicated that mesenchymal-like cancer cells displaying high motility and low adhesion proliferate more rapidly and display a survival advantage over epithelial-like cancer cells. Furthermore, the presence of mesenchymal-like cells within the primary tumor influences the macroscopic properties, emergent morphology, and growth rate of tumors. PMID:22566967

  14. Silencing of p130Cas in Ovarian Carcinoma: A Novel Mechanism for Tumor Cell Death

    PubMed Central

    Nick, Alpa M.; Stone, Rebecca L.; Armaiz-Pena, Guillermo; Ozpolat, Bulent; Tekedereli, Ibrahim; Graybill, Whitney S.; Landen, Charles N.; Villares, Gabriel; Vivas-Mejia, Pablo; Bottsford-Miller, Justin; Kim, Hye Sun; Lee, Ju-Seog; Kim, Soo Mi; Baggerly, Keith A.; Ram, Prahlad T.; Deavers, Michael T.; Coleman, Robert L.; Lopez-Berestein, Gabriel

    2011-01-01

    Background We investigated the clinical and biological significance of p130cas, an important cell signaling molecule, in ovarian carcinoma. Methods Expression of p130cas in ovarian tumors, as assessed by immunohistochemistry, was associated with tumor characteristics and patient survival. The effects of p130cas gene silencing with small interfering RNAs incorporated into neutral nanoliposomes (siRNA-DOPC), alone and in combination with docetaxel, on in vivo tumor growth and on tumor cell proliferation (proliferating cell nuclear antigen) and apoptosis (terminal deoxynucleotidyl transferase dUTP nick-end labeling) were examined in mice bearing orthotopic taxane-sensitive (HeyA8 and SKOV3ip1) or taxane-resistant (HeyA8-MDR) ovarian tumors (n = 10 per group). To determine the specific mechanisms by which p130cas gene silencing abrogates tumor growth, we measured cell viability (MTT assay), apoptosis (fluorescence-activated cell sorting), autophagy (immunoblotting, fluorescence, and transmission electron microscopy), and cell signaling (immunoblotting) in vitro. All statistical tests were two-sided. Results Of 91 ovarian cancer specimens, 70 (76%) had high p130cas expression; and 21 (24%) had low p130cas expression. High p130cas expression was associated with advanced tumor stage (P < .001) and higher residual disease (>1 cm) following primary cytoreduction surgery (P = .007) and inversely associated with overall survival and progression-free survival (median overall survival: high p130cas expression vs low expression, 2.14 vs 9.1 years, difference = 6.96 years, 95% confidence interval = 1.69 to 9.48 years, P < .001; median progression-free survival: high p130cas expression vs low expression, 1.04 vs 2.13 years, difference = 1.09 years, 95% confidence interval = 0.47 to 2.60 years, P = .01). In mice bearing orthotopically implanted HeyA8 or SKOV3ip1 ovarian tumors, treatment with p130cas siRNA-DOPC in combination with docetaxel chemotherapy resulted in the greatest

  15. Tumor budding predicts response to anti-EGFR therapies in metastatic colorectal cancer patients

    PubMed Central

    Zlobec, Inti; Molinari, Francesca; Martin, Vittoria; Mazzucchelli, Luca; Saletti, Piercarlo; Trezzi, Rosangela; De Dosso, Sara; Vlajnic, Tatjana; Frattini, Milo; Lugli, Alessandro

    2010-01-01

    AIM: To investigate whether the evaluation of tumor budding can complement K-RAS analysis to improve the individualized prediction of response to anti-epidermal growth factor receptor based therapies in metastatic colorectal cancer (mCRC) patients. METHODS: Forty-three patients with mCRC treated with cetuximab or panitumumab were entered into this study. According to the Response Evaluation Criteria in Solid Tumors criteria, 30 patients had stable or progressive disease (non-responsive), while 13 patients had a partial response. Tumor buds were evaluated from whole tissue sections stained for pan-cytokeratin, evaluated in the densest region using a 40 × objective and “high-grade” tumor budding was defined as 15 buds/high-power field. RESULTS: Tumor buds and K-RAS mutation both correctly classified 68% of patients. All patients with K-RAS mutation (n = 7) or high-grade tumor budding (n = 11) were non-responsive, of which 4 patients had both features. All 13 partial responders were K-RAS wild-type with low-grade tumor budding. Combined, the predictive value of K-RAS and tumor budding was 80%. Additionally, high-grade tumor budding was significantly related to worse progression-free survival [HR (95% CI): 2.8 (1.3-6.0, P = 0.008)]. CONCLUSION: If confirmed in larger cohorts, the addition of tumor budding to K-RAS analysis may represent an effective approach for individualized patient management in the metastatic setting. PMID:20939111

  16. A novel somatic MAPK1 mutation in primary ovarian mixed germ cell tumors.

    PubMed

    Zou, Yang; Deng, Wei; Wang, Feng; Yu, Xiao-Hong; Liu, Fa-Ying; Yang, Bi-Cheng; Huang, Mei-Zhen; Guo, Jiu-Bai; Xie, Qiu-Hua; He, Ming; Huang, Ou-Ping

    2016-02-01

    A recent exome-sequencing study revealed prevalent mitogen-activated protein kinase 1 (MAPK1) p.E322K mutation in cervical carcinoma. It remains largely unknown whether ovarian carcinomas also harbor MAPK1 mutations. As paralogous gene mutations co‑occur frequently in human malignancies, we analyzed here a total of 263 ovarian carcinomas for the presence of MAPK1 and paralogous MAPK3 mutations by DNA sequencing. A previously unreported MAPK1 p.D321N somatic mutation was identified in 2 out of 18 (11.1%) ovarian mixed germ cell tumors, while no other MAPK1 or MAPK3 mutation was detected in our samples. Of note, OCC‑115, the MAPK1‑mutated sample with bilateral cancerous ovaries affected, harbored MAPK1 mutation in the right ovary while retained the left ovary intact, implicating that the genetic alterations underlying ovarian mixed germ cell tumor may be different, even in patients with similar genetic backgrounds and tumor microenvironments. The results of evolutionary conservation and protein structure modeling analysis implicated that MAPK1 p.D321N mutation may be pathogenic. Additionally, mutations in protein phosphatase 2 regulatory subunit α (PPP2R1A), ring finger protein 43 (RNF43), DNA directed polymerase ε (POLE1), ribonuclease type III (DICER1), CCCTC‑binding factor (CTCF), ribosomal protein L22 (RPL22), DNA methyltransferase 3α (DNMT3A), transformation/transcription domain‑associated protein (TRRAP), isocitrate dehydrogenase (IDH)1 and IDH2 were not detected in ovarian mixed germ cell tumors, implicating these genetic alterations may be not associated with MAPK1 mutation in the development of this malignancy. The present study identified a previously unreported MAPK1 mutation in ovarian mixed germ cell tumors for the first time, and this mutation may be actively involved in the tumorigenesis of this disease. PMID:26548627

  17. Virilizing Ovarian Steroid Cell Tumor: A Rare Case

    PubMed Central

    Rangaiah, Nagarathnamma; Prasad, Nagendra; Channaveeregowda, Savitha

    2015-01-01

    Ovarian steroid cell tumours are fewer than 5 percent of sex-cord stromal tumours and 0.1% of all ovarian tumours. The average age at diagnosis is the mid-20s, but patients can present at virtually any age. We present a case of 38-year-old multipara with history of secondary amenorrhea, clinical signs & symptoms of virilization developed over the past 5 years. With elevated (115ng/dL) serum testosterone level and radiological findings of a left adnexal solid mass; the patient was suspected to have a virilizing tumour of left ovary. Laparoscopic left salpingo-oophorectomy was performed. Histopathology revealed tumour cells in small nests with vacuolated to eosinophilic cytoplasm with nuclear atypia completely replacing the ovarian tissue suggestive of steroid cell tumour (NOS) of ovary. The patient was discharged and advised for follow up with serum testosterone levels after 3 weeks. PMID:26500963

  18. Chemotherapy and irradiation for locally advanced and metastatic pulmonary carcinoid tumors

    PubMed Central

    Chong, Curtis R.; Wirth, Lori J.; Nishino, Mizuki; Chen, Aileen B.; Sholl, Lynette M.; Kulke, Matthew H.; McNamee, Ciaran J.; Jänne, Pasi A.; Johnson, Bruce E.

    2015-01-01

    Objectives The optimal management of locally advanced and metastatic pulmonary carcinoid tumors remains to be determined. Materials and methods A retrospective review was conducted on patients with typical and atypical pulmonary carcinoid tumors treated at our institutions between 1990 and 2012. Results 300 patients were identified with pulmonary carcinoid, (80 patients with atypical carcinoid), of whom 29 presented with metastatic disease (16 atypical). Of evaluable patients, 26 (41%) with stages I–III atypical carcinoid tumors recurred at a median time of 3.7 years (range, 0.4–32), compared to 3 (1%) patients with typical carcinoid (range, 8–12.3). 39 patients were treated with chemotherapy, including 30 patients with metastatic disease (27 atypical), and 7 patients were treated with adjuvant platinum–etoposide chemoradiation (6 atypical, 1 typical, 6 stage IIIA, 1 stage IIB). At a median follow-up of 2 years there were 2 recurrences in the 7 patients receiving adjuvant treatment. Median survival after diagnosis of metastatic disease for patients with atypical pulmonary carcinoid was 3.3 years with a 5-year survival of 24%. Treatment regimens showing efficacy in pulmonary carcinoid include 15 patients treated with octreotide-based therapies (10% response rate (RR), 70% disease control rate (DCR), 15 month median progression-free survival (PFS)), 13 patients treated with etoposide + platinum (23% RR, 69% DCR, 7 month median PFS), and 14 patients treated with temozolomide-based therapies (14% RR, 57% DCR, 10 month median PFS). 8 of 10 patients with octreotide-avid disease treated with an octreotide-based regimen experienced disease control (1 partial response, 7 stable disease) for a median of 18 months (range 6–72 months). Conclusions These results support our previous finding that a subset of pulmonary carcinoid tumors are responsive to chemotherapy. PMID:25218177

  19. MV-NIS Infected Mesenchymal Stem Cells in Treating Patients With Recurrent Ovarian Cancer

    ClinicalTrials.gov

    2016-07-08

    Malignant Ovarian Brenner Tumor; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Ovarian Carcinoma

  20. Management of bilateral malignant ovarian germ cell tumors: Experience of a single institute

    PubMed Central

    Zhao, Ting; Liu, Yan; Jiang, Hongyuan; Zhang, Hao; Lu, Yuan

    2016-01-01

    Bilateral malignant ovarian germ cell tumors (MOGCTs) are rare. Determination of the optimal treatment modalities is crucial, as these malignancies mainly affect girls and young women who may wish to preserve their fertility. In order to review the prevalence, clinical characteristics, treatment and outcome of bilateral MOGCTs, we performed a retrospective review of patients who were diagnosed with bilateral MOGCTs and underwent primary surgery at the Obstetrics and Gynecology Hospital of Fudan University (Shanghai, China) between January, 2001 and December, 2014. Of the 130 patients investigated, 8 were diagnosed with bilateral disease, most of whom were International Federation of Gynecology and Obstetrics stage I. There was no significant difference in overall and disease-free survival between patients with unilateral and those with bilateral disease. Cases with dysgerminoma, dysgerminoma coexisting with gonadoblastoma, yolk sac tumor and ovarian primary choriocarcinoma were included in this study. Fertility was spared in 2 patients (1 with dysgerminoma and 1 with ovarian primary choriocarcinoma). The patient with ovarian choriocarcinoma experienced relapse and was finally salvaged by radical surgery and adjuvant chemotherapy. According to our results and the published data, patients affected by bilateral MOGCTs have a satisfactory prognosis. The treatment modalities largely depend on the histological type of the tumor. Fertility-sparing surgery may be safe for patients affected by dysgerminoma, but should be considered with caution in patients with ovarian primary choriocarcinoma. PMID:27446585

  1. Predicting Ovarian Cancer Patients' Clinical Response to Platinum-Based Chemotherapy by Their Tumor Proteomic Signatures.

    PubMed

    Yu, Kun-Hsing; Levine, Douglas A; Zhang, Hui; Chan, Daniel W; Zhang, Zhen; Snyder, Michael

    2016-08-01

    Ovarian cancer is the deadliest gynecologic malignancy in the United States with most patients diagnosed in the advanced stage of the disease. Platinum-based antineoplastic therapeutics is indispensable to treating advanced ovarian serous carcinoma. However, patients have heterogeneous responses to platinum drugs, and it is difficult to predict these interindividual differences before administering medication. In this study, we investigated the tumor proteomic profiles and clinical characteristics of 130 ovarian serous carcinoma patients analyzed by the Clinical Proteomic Tumor Analysis Consortium (CPTAC), predicted the platinum drug response using supervised machine learning methods, and evaluated our prediction models through leave-one-out cross-validation. Our data-driven feature selection approach indicated that tumor proteomics profiles contain information for predicting binarized platinum response (P < 0.0001). We further built a least absolute shrinkage and selection operator (LASSO)-Cox proportional hazards model that stratified patients into early relapse and late relapse groups (P = 0.00013). The top proteomic features indicative of platinum response were involved in ATP synthesis pathways and Ran GTPase binding. Overall, we demonstrated that proteomic profiles of ovarian serous carcinoma patients predicted platinum drug responses as well as provided insights into the biological processes influencing the efficacy of platinum-based therapeutics. Our analytical approach is also extensible to predicting response to other antineoplastic agents or treatment modalities for both ovarian and other cancers. PMID:27312948

  2. The Fractalkine-Receptor Axis Improves Human Colorectal Cancer Prognosis by Limiting Tumor Metastatic Dissemination.

    PubMed

    Erreni, Marco; Siddiqui, Imran; Marelli, Giulia; Grizzi, Fabio; Bianchi, Paolo; Morone, Diego; Marchesi, Federica; Celesti, Giuseppe; Pesce, Samantha; Doni, Andrea; Rumio, Cristiano; Roncalli, Massimo G; Laghi, Luigi; Mantovani, Alberto; Allavena, Paola

    2016-01-15

    Human colorectal cancer (CRC) is a frequent neoplasia in Western countries, and its metastatic progression is a major cause of cancer-related death. In search of specific molecules upregulated in CRC, with possible clinical relevance, we performed a differential gene-profiling analysis in surgery-derived CRC samples and adjacent uninvolved intestinal mucosa. The chemokine CX3CL1 and its specific receptor CX3CR1 were significantly upregulated in tumors. Higher expression of CX3CL1 and CX3CR1 was confirmed by immunohistochemistry in 100 CRC tumor samples (stages I-III). Unexpectedly, high immune scores of CX3CL1 did not correlate with the density of tumor-infiltrating CD3(+) T cells or CD68(+) macrophages. Coexpression of ligand and receptor by tumor cells (axis-positive tumors) significantly associated with longer disease-free (p = 0.01) and disease-specific survival (p = 0.001). Conversely, axis-negative tumors (with low expression of both ligand and receptor) had increased risk of tumor relapse (p = 0.02), and increased likelihood of metachronous metastasis (p = 0.001), including after stage adjustment (p = 0.006). Transduction of CX3CL1 and CX3CR1 in CRC tumor cell lines induced cell aggregation that strongly inhibited in vitro migration in chemotaxis assays. In a mouse model of spleen-liver metastases, cancer dissemination to liver was dramatically reduced in CX3CL1-CX3CR1-expressing tumors, and ligand-receptor interaction was confirmed in cancer cells in vivo by fluorescence resonance energy transfer analysis. In conclusion, tumoral expression of the CX3CL1-CX3CR1 chemokine axis functions as a retention factor, increasing homotypic cell adhesion and limiting tumor spreading to metastatic sites. Lack or low levels of expression of CX3CL1-CX3CR1 by tumor cells identifies a group of CRC patients at increased risk of metastatic progression. PMID:26673138

  3. Curculigoside augments cell-mediated immune responses in metastatic tumor-bearing animals.

    PubMed

    Murali, Vishnu Priya; Kuttan, Girija

    2016-08-01

    A positive modulation of immune system is necessary for preparing the body to fight against malignant tumor cells. In the present study, the stimulatory effect of Curculigoside on cell-mediated immune response against the metastasis of B16F10 melanoma cells was analyzed in C57BL/6 mice. Curculigoside is a phenolic glucoside present in the plant Curculigo orchioides Gaertn. (Family - Amaryllidaceae). Administration of Curculigoside enhanced the natural killer (NK) cell activity, antibody-dependent cell-mediated cytotoxicity and complement-mediated cytotoxicity in metastatic tumor-bearing animals, when compared to the untreated control animals. The compound was also found to be effective in reducing the levels of proinflammatory cytokines such as TNF-α, IL-1β, IL-6 and GM-CSF during metastasis. Besides these, levels of TH1 cytokines, such as IL-2 and IFN-γ, were significantly enhanced (p < 0.001) by Curculigoside administration and thereby reduces the metastatic lung colony formation along with an increased lifespan of the experimental animals. These studies provide an evidence for the stimulation of cell-mediated immune responses by Curculigoside against B16F10-induced metastatic tumor progression in experimental animals. PMID:27228189

  4. Trismus and diffuse polymyalgia: an unusual presentation of recurrent metastatic ovarian cancer.

    PubMed

    Benjamin, Ramsis; Zhai, Jing; Morgan, Robert; Prakash, Neal

    2014-01-01

    A 22-year-old woman first presented in 2009 with abdominal distention. The diagnosis of stage IA right ovarian tumour was made by fertility-sparing surgery. In the subsequent years, the involvement of the left ovary and metastasis to the lungs prompted further surgical intervention and chemotherapy. By 2013, she experienced insidious, debilitating and diffuse musculoskeletal pain with trismus. Polymyositis or diffuse radiculitis was suspected. Imaging studies identified enhancing lesions in the thigh musculature, temporalis, parotid gland, pterygoid, masseter, tongue, cerebellum and leptomeninges. Biopsy of one of the thigh lesions confirmed the diagnosis of mucinous adenocarcinoma. She succumbed to the disease in November 2013. This case illustrates the aggressive nature of mucinous epithelial ovarian cancer and its resilience to conventional chemotherapy. On account of its high death rate, it is recommended that the epithelial-mesenchymal transition be researched and early therapy targeted at the k-ras oncogene initiated in spite of the tumour's lower initial staging. PMID:24835804

  5. Trismus and diffuse polymyalgia: an unusual presentation of recurrent metastatic ovarian cancer

    PubMed Central

    Benjamin, Ramsis; Zhai, Jing; Morgan, Robert; Prakash, Neal

    2014-01-01

    A 22-year-old woman first presented in 2009 with abdominal distention. The diagnosis of stage IA right ovarian tumour was made by fertility-sparing surgery. In the subsequent years, the involvement of the left ovary and metastasis to the lungs prompted further surgical intervention and chemotherapy. By 2013, she experienced insidious, debilitating and diffuse musculoskeletal pain with trismus. Polymyositis or diffuse radiculitis was suspected. Imaging studies identified enhancing lesions in the thigh musculature, temporalis, parotid gland, pterygoid, masseter, tongue, cerebellum and leptomeninges. Biopsy of one of the thigh lesions confirmed the diagnosis of mucinous adenocarcinoma. She succumbed to the disease in November 2013. This case illustrates the aggressive nature of mucinous epithelial ovarian cancer and its resilience to conventional chemotherapy. On account of its high death rate, it is recommended that the epithelial–mesenchymal transition be researched and early therapy targeted at the k-ras oncogene initiated in spite of the tumour's lower initial staging. PMID:24835804

  6. Ultrasound diagnosis of serous surface papillary borderline ovarian tumor: A case series with a review of the literature.

    PubMed

    Ludovisi, Manuela; Foo, Xulin; Mainenti, Sara; Testa, Antonia Carla; Arora, Rupali; Jurkovic, Davor

    2015-01-01

    Serous surface papillary borderline ovarian tumors (SSPBOTs) are a rare morphologic variant of serous ovarian tumors that are typically confined to the ovarian surface, while the ovaries themselves tend to appear normal in size and shape. In this report, we describe the findings from five premenopausal women diagnosed with SSPBOTs, in whom ultrasound showed grossly normal ovaries that were partially or wholly covered with irregular solid tumors. In all five cases, histologic examination showed evidence of borderline serous tumors. These findings demonstrate that SSPBOTs can be diagnosed on a preoperative sonographic examination, which could facilitate conservative, fertility-sparing surgery in young women affected by this condition. PMID:25706035

  7. Assessment of Tumor Radioresponsiveness and Metastatic Potential by Dynamic Contrast-Enhanced Magnetic Resonance Imaging

    SciTech Connect

    Ovrebo, Kirsti Marie; Gulliksrud, Kristine; Mathiesen, Berit; Rofstad, Einar K.

    2011-09-01

    Purpose: It has been suggested that gadolinium diethylene-triamine penta-acetic acid (Gd-DTPA)-based dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) may provide clinically useful biomarkers for personalized cancer treatment. In this preclinical study, we investigated the potential of DCE-MRI as a noninvasive method for assessing the radioresponsiveness and metastatic potential of tumors. Methods and Materials: R-18 melanoma xenografts growing in BALB/c nu/nu mice were used as experimental tumor models. Fifty tumors were subjected to DCE-MRI, and parametric images of K{sup trans} (the volume transfer constant of Gd-DTPA) and v{sub e} (the fractional distribution volume of Gd-DTPA) were produced by pharmacokinetic analysis of the DCE-MRI series. The tumors were irradiated after the DCE-MRI, either with a single dose of 10 Gy for detection of radiobiological hypoxia (30 tumors) or with five fractions of 4 Gy in 48 h for assessment of radioresponsiveness (20 tumors). The host mice were then euthanized and examined for lymph node metastases, and the primary tumors were resected for measurement of cell survival in vitro. Results: Tumors with hypoxic cells showed significantly lower K{sup trans} values than tumors without significant hypoxia (p < 0.0001, n = 30), and K{sup trans} decreased with increasing cell surviving fraction for tumors given fractionated radiation treatment (p < 0.0001, n = 20). Tumors in metastasis-positive mice had significantly lower K{sup trans} values than tumors in metastasis-negative mice (p < 0.0001, n = 50). Significant correlations between v{sub e} and tumor hypoxia, radioresponsiveness, or metastatic potential could not be detected. Conclusions: R-18 tumors with low K{sup trans} values are likely to be resistant to radiation treatment and have a high probability of developing lymph node metastases. The general validity of these observations should be investigated further by studying preclinical tumor models with biological

  8. High concordance of ALK rearrangement between primary tumor and paired metastatic lymph node in patients with lung adenocarcinoma

    PubMed Central

    Hou, Likun; Ren, Shengxiang; Su, Bo; Zhang, Liping; Wu, Wei; Zhang, Wei; Dong, Zhengwei; Huang, Yan

    2016-01-01

    Background Lung cancer has heterogeneous features. It remains unclear whether ALK rearrangement was distributed heterogeneously in tumor from different anatomic sites. To address this issue, we investigate the concordance of ALK rearrangement between primary tumors and paired metastatic lymph nodes in pulmonary adenocarcinoma patients. Methods From Sep 2013 to May 2014, resectable lung adenocarcinoma patients with EGFR wildtype and paired metastatic lymph nodes from Tongji University affiliated Shanghai pulmonary hospital were selected into this study. An auto-mated Ventana ALK with clone D5F3 antibody immunohistochemistry (IHC) and reverse transcriptase-polymerase chain reaction (RT-PCR) were used to detected ALK rearrangement. Discordant cases between IHC and RT-PCR were further validated by fluorescence in situ hybridization (FISH). Results A total of 101 patients were enrolled into this study with a median age of 60 years old (range, 35–78 years). ALK rearrangement was found in 20 primary lesions, while in 18 paired metastatic lymph nodes. ALK rearrangement was more frequently happened in younger (P<0.001), Nonsmokers (P=0.012), high-stage disease (P=0.021) and predominantly solid growth pattern (P=0.024). The concordance rate between primary tumor and paired metastatic lymph nodes was 98%. Two patients with ALK rearrangement on primary tumor didn’t show ALK gene fusion on paired metastatic lymph nodes. Sixty-eight cases had more than two stations of metastatic lymph nodes. ALK rearrangement in the different station of metastatic lymph nodes of the same patient was consistent. Conclusions High concordant rate of ALK rearrangement between primary tumors and paired metastatic lymph nodes were found in this study. The authors concluded that specimens from metastatic lesions and primary tumors are equally suitable for detection ALK rearrangement. PMID:27293826

  9. New construction of an animal model for the orthotopic transplantation of an ovarian tumor.

    PubMed

    Zhang, Hui; Gao, Xinping; Yang, Yongan; Wang, Weiming; Liu, Jin; Liang, Yijuan; Wu, Hongli; Qin, Jinjin; Pan, Kun; Wang, Yifeng; Shi, Junrong; Ma, Youju

    2014-01-01

    A new technique has successfully established the non-obese diabetic/severely combined immunodeficiency (NOD/SCID) mouse model of ovarian cancer. Under 4% chloral hydrate (0.1 mL/g dose) anesthesia, female mice were inoculated with tumor-cell suspension. The expression rate of OVCAR3 to CA125 was assessed using flow cytometry. The inoculated site was hand palpated and the signs and symptoms related to tumor growth were observed with the naked eye. The allophycocyanin (APC) indirectly labeled mouse-antihuman CA125 and fluorescein isothiocyanate (FITC)-labeled anti-mouse MHC Class I molecule (H-2K(d)/H-2D(d)) were observed using a confocal laser scanning microscope. The animal model of ovarian cancer constructed using this method can more directly reflect the characteristics of cancer cells. It provides reliable experimental results and presents a technical platform for the research of ovarian cancer stem cells. PMID:24955132

  10. New construction of an animal model for the orthotopic transplantation of an ovarian tumor

    PubMed Central

    2014-01-01

    A new technique has successfully established the non-obese diabetic/severely combined immunodeficiency (NOD/SCID) mouse model of ovarian cancer. Under 4% chloral hydrate (0.1 mL/g dose) anesthesia, female mice were inoculated with tumor-cell suspension. The expression rate of OVCAR3 to CA125 was assessed using flow cytometry. The inoculated site was hand palpated and the signs and symptoms related to tumor growth were observed with the naked eye. The allophycocyanin (APC) indirectly labeled mouse-antihuman CA125 and fluorescein isothiocyanate (FITC)-labeled anti-mouse MHC Class I molecule (H-2Kd/H-2Dd) were observed using a confocal laser scanning microscope. The animal model of ovarian cancer constructed using this method can more directly reflect the characteristics of cancer cells. It provides reliable experimental results and presents a technical platform for the research of ovarian cancer stem cells. PMID:24955132

  11. Ovarian cancer treatment with a tumor-targeting and gene expression-controllable lipoplex

    PubMed Central

    He, Zhi-Yao; Deng, Feng; Wei, Xia-Wei; Ma, Cui-Cui; Luo, Min; Zhang, Ping; Sang, Ya-Xiong; Liang, Xiao; Liu, Li; Qin, Han-Xiao; Shen, Ya-Li; Liu, Ting; Liu, Yan-Tong; Wang, Wei; Wen, Yan-Jun; Zhao, Xia; Zhang, Xiao-Ning; Qian, Zhi-Yong; Wei, Yu-Quan

    2016-01-01

    Overexpression of folate receptor alpha (FRα) and high telomerase activity are considered to be the characteristics of ovarian cancers. In this study, we developed FRα-targeted lipoplexes loaded with an hTERT promoter-regulated plasmid that encodes a matrix protein (MP) of the vesicular stomatitis virus, F-LP/pMP(2.5), for application in ovarian cancer treatment. We first characterized the pharmaceutical properties of F-LP/pMP(2.5). The efficient expression of the MP-driven hTERT promoter in SKOV-3 cells was determined after an in-vitro transfection assay, which was significantly increased compared with a non-modified LP/pMP(2.5) group. F-LP/pMP(2.5) treatment significantly inhibited the growth of tumors and extended the survival of mice in a SKOV-3 tumor model compared with other groups. Such an anti-tumor effect was due to the increased expression of MP in tumor tissue, which led to the induction of tumor cell apoptosis, inhibition of tumor cell proliferation and suppression of tumor angiogenesis. Furthermore, a preliminary safety evaluation demonstrated a good safety profile of F-LP/pMP(2.5) as a gene therapy agent. Therefore, FRα-targeted lipoplexes with therapeutic gene expression regulated by an hTERT promoter might be a promising gene therapy agent and a potential translational candidate for the clinical treatment of ovarian cancer. PMID:27026065

  12. Ovarian cancer treatment with a tumor-targeting and gene expression-controllable lipoplex.

    PubMed

    He, Zhi-Yao; Deng, Feng; Wei, Xia-Wei; Ma, Cui-Cui; Luo, Min; Zhang, Ping; Sang, Ya-Xiong; Liang, Xiao; Liu, Li; Qin, Han-Xiao; Shen, Ya-Li; Liu, Ting; Liu, Yan-Tong; Wang, Wei; Wen, Yan-Jun; Zhao, Xia; Zhang, Xiao-Ning; Qian, Zhi-Yong; Wei, Yu-Quan

    2016-01-01

    Overexpression of folate receptor alpha (FRα) and high telomerase activity are considered to be the characteristics of ovarian cancers. In this study, we developed FRα-targeted lipoplexes loaded with an hTERT promoter-regulated plasmid that encodes a matrix protein (MP) of the vesicular stomatitis virus, F-LP/pMP(2.5), for application in ovarian cancer treatment. We first characterized the pharmaceutical properties of F-LP/pMP(2.5). The efficient expression of the MP-driven hTERT promoter in SKOV-3 cells was determined after an in-vitro transfection assay, which was significantly increased compared with a non-modified LP/pMP(2.5) group. F-LP/pMP(2.5) treatment significantly inhibited the growth of tumors and extended the survival of mice in a SKOV-3 tumor model compared with other groups. Such an anti-tumor effect was due to the increased expression of MP in tumor tissue, which led to the induction of tumor cell apoptosis, inhibition of tumor cell proliferation and suppression of tumor angiogenesis. Furthermore, a preliminary safety evaluation demonstrated a good safety profile of F-LP/pMP(2.5) as a gene therapy agent. Therefore, FRα-targeted lipoplexes with therapeutic gene expression regulated by an hTERT promoter might be a promising gene therapy agent and a potential translational candidate for the clinical treatment of ovarian cancer. PMID:27026065

  13. Recovery from Choriocarcinoma Syndrome Associated with a Metastatic Extragonadal Germ Cell Tumor Hemorrhage.

    PubMed

    Komori, Koji; Takahari, Daisuke; Kimura, Kenya; Kinoshita, Takashi; Ito, Seiji; Abe, Tetsuya; Senda, Yoshiki; Misawa, Kazunari; Ito, Yuichi; Uemura, Norihisa; Natsume, Seiji; Kawakami, Jiro; Iwata, Yoshinori; Tsutsuyama, Masayuki; Shigeyoshi, Itaru; Akazawa, Tomoyuki; Hayashi, Daisuke; Ouchi, Akira; Shimizu, Yasuhiro

    2016-01-01

    A germ cell tumor is the most common form of malignancy in early male life, and can be classified as either seminomatous or nonseminomatous. Choriocarcinoma, comprised of nonseminomatous germ cells, is the most aggressive type of germ cell tumor and characteristically metastasizes to the retroperitoneal lymph nodes and less frequently to the lungs, liver, bone or brain [Shibuya et al., 2009;48: 551-554]. A 56-year-old man was admitted to another hospital complaining of abdominal distension. Symptoms included anorexia, vomiting, and diarrhea. The patient was diagnosed with an extragonadal germ cell tumor and referred to our hospital to receive chemotherapy. The day after admission, the patient's abdominal distension gradually worsened. An emergency operation revealed venous hemorrhage from the surface of a metastatic extragonadal germ cell tumor between the ligament of Treitz and the inferior mesenteric vein in a horizontal position. Hemostatic treatment was performed with 4-0 proline thread attached to a medicated cotton sponge, rather than using a simple proline thread, and the closure area was manually compressed. Chemotherapy was initiated on postoperative day 10. A metastatic extragonadal germ cell tumor that causes massive hemorrhage and gastrointestinal hemorrhage is very rare, and represents a life-threatening emergency. If the patient's condition carries a substantial risk of bleeding to death, it may be worthwhile to attempt abdominal operations. PMID:27403124

  14. Recovery from Choriocarcinoma Syndrome Associated with a Metastatic Extragonadal Germ Cell Tumor Hemorrhage

    PubMed Central

    Komori, Koji; Takahari, Daisuke; Kimura, Kenya; Kinoshita, Takashi; Ito, Seiji; Abe, Tetsuya; Senda, Yoshiki; Misawa, Kazunari; Ito, Yuichi; Uemura, Norihisa; Natsume, Seiji; Kawakami, Jiro; Iwata, Yoshinori; Tsutsuyama, Masayuki; Shigeyoshi, Itaru; Akazawa, Tomoyuki; Hayashi, Daisuke; Ouchi, Akira; Shimizu, Yasuhiro

    2016-01-01

    A germ cell tumor is the most common form of malignancy in early male life, and can be classified as either seminomatous or nonseminomatous. Choriocarcinoma, comprised of nonseminomatous germ cells, is the most aggressive type of germ cell tumor and characteristically metastasizes to the retroperitoneal lymph nodes and less frequently to the lungs, liver, bone or brain [Shibuya et al., 2009;48: 551–554]. A 56-year-old man was admitted to another hospital complaining of abdominal distension. Symptoms included anorexia, vomiting, and diarrhea. The patient was diagnosed with an extragonadal germ cell tumor and referred to our hospital to receive chemotherapy. The day after admission, the patient's abdominal distension gradually worsened. An emergency operation revealed venous hemorrhage from the surface of a metastatic extragonadal germ cell tumor between the ligament of Treitz and the inferior mesenteric vein in a horizontal position. Hemostatic treatment was performed with 4-0 proline thread attached to a medicated cotton sponge, rather than using a simple proline thread, and the closure area was manually compressed. Chemotherapy was initiated on postoperative day 10. A metastatic extragonadal germ cell tumor that causes massive hemorrhage and gastrointestinal hemorrhage is very rare, and represents a life-threatening emergency. If the patient's condition carries a substantial risk of bleeding to death, it may be worthwhile to attempt abdominal operations.

  15. Retroperitoneal metastatic germ cell tumor presenting as a psoas abscess: a diagnostic pitfall.

    PubMed

    Dieker, Carrie A; De Las Casas, Luis E; Davis, Brian R

    2013-07-01

    Most testicular neoplasms are germ cell tumors, the vast majority of which represent seminomas. Most seminomas present localized to the testis, whereas nonseminomatous germ cell tumors more often present with lymph node metastases. Psoas abscesses generally arise from a contiguous intra-abdominal or pelvic infectious process, an adjacent focus of osteomyelitis or septic emboli from distant infectious foci. In this study, the case of a 24-year-old man who presented with a right psoas mass presumptively diagnosed as an abscess secondary to fever and leukocytosis is presented. The patient had a history of right testicular seminoma, and normal serum levels of alpha-fetoprotein and human chorionic gonadotropin. Surgical exploration and biopsy demonstrated seminoma metastasis. This case represents an extremely unusual clinical presentation of metastatic germ cell tumor presenting as a psoas abscess. This unique case represents an unusual presentation of a recurrent germ cell tumor mimicking a psoas abscess. Awareness of possible metastatic testicular germ cell neoplasm as a psoas abscess could prevent diagnosis delay before retroperitoneal tumor debulking. PMID:23360792

  16. Patient-derived tumor xenograft strategies for informed management of patients with metastatic melanoma.

    PubMed

    Qassemyar, Ahmad; Gabert, Pierre-Elliott; Kluza, Jerome; Duquennoy-Martinot, Véronique; Mortier, Laurent; Marchetti, Philippe; Guerreschi, Pierre

    2016-06-01

    Metastatic melanoma has benefited from immunotherapy and targeted therapy advances. Faced with the inescapable onset of treatment resistance, the choice of a second-line treatment can be guided by a patient-derived tumor xenograft (PDTX). This new approach requires an excellent multidisciplinary collaboration where the surgeon has a key role to play. Each patient included (stage IIIC or IV) presented with subcutaneous melanoma metastasis that could be surgically resected. The surgeon performed orthotopic PDTX on CB17-SCID mice. To validate the model, tumor material was amplified over three successive generations of animals to obtain cohorts compatible with carrying out a study to compare treatment response by targeted therapy (vemurafenib versus controls). Tumors were characterized (histologically and genetically) at all stages of the generations' amplification. Functional imaging by fluorine-18 fluorodeoxyglucose PET scan was performed for the third generation PDTX. Seventeen patients with a mutated BRAF V600E subcutaneous metastasis were included, yielding 257 PDTX. Clinical, histological, and genetic characteristics of the grafted tumors were stable over the three mice generations. The treatment response to vemurafenib was observed for all PDTX. The fluorine-18 fluorodeoxyglucose PET scan evidenced a decreased in glucose uptake in the treated tumors. PDTX models are being widely used in fundamental research and are more compatible with clinical issues. If PDTX are simple and easily reproducible in metastatic melanoma, an organized multidisciplinary platform is essential to implement them. In our experience, surgeons have a key role to play in the cohesion of this new therapeutic approach. PMID:26983079

  17. Ovarian Tumors in Children and Adolescents: A 10-Yr Histopathologic Review in Korle-Bu Teaching Hospital, Ghana.

    PubMed

    Akakpo, Patrick K; Derkyi-Kwarteng, Leonard; Quayson, Solomon E; Gyasi, Richard K; Anim, Jehoram T

    2016-07-01

    To determine the histopathologic types, frequency of occurrence, age distribution, presenting signs, and symptoms of ovarian tumors in children and adolescents diagnosed at the Korle-Bu Teaching Hospital all histopathology slides and request cards of ovarian tumors diagnosed in subjects aged, 0 to 19 yr over a 10-yr period (2001-2010) were reviewed. Biographical and clinical data of the patients were collected. The results were entered into Epi-info to determine the frequency of various ovarian tumors in different age groups and their association with presenting signs and symptoms. A total of 67 (9.5%) ovarian tumors were diagnosed in patients aged 0 to 19 yr of a total of 706 diagnosed in all age groups during the period. The majority [44 (65.7%)] were germ cell tumors, the commonest being mature cystic teratoma. Burkitt lymphoma was the single most common malignant tumor, comprising 6(9%) of all the tumors, although as a group malignant germ cell tumors were still the most common malignant ovarian tumors in children and adolescents. Although germ cell tumors were the most common tumors in this age group (both benign and malignant), Burkitt lymphoma, a peculiar malignant tumor in this subregion, was the single most common malignant tumor of the ovary. PMID:26630227

  18. Bleomycin-Induced Flagellate Erythema in a Patient Diagnosed with Ovarian Yolk Sac Tumor

    PubMed Central

    Boussios, Stergios; Moschetta, Michele; McLachlan, Jennifer; Banerjee, Susana

    2015-01-01

    Flagellate linear hyperpigmentation can rarely be caused by the chemotherapy agent, bleomycin. Herein, we describe the case of a 20-year-old woman treated with bleomycin for an ovarian yolk sac tumor and review the prominent features of this form of dermatitis. PMID:26798532

  19. Combined Adrenal and Ovarian Venous Sampling to Localize an Androgen Producing Tumor

    SciTech Connect

    Agarwal, Monica D.; Trerotola, Scott O.

    2010-12-15

    A postmenopausal woman presented with hirsutism and elevated serum testosterone levels. A 1-cm adrenal adenoma was noted on computed tomography. Combined adrenal and ovarian venous sampling was performed to localize an androgen producing tumor to the left ovary. The patient underwent a bilateral salpingo-oophrectomy and was spared an unnecessary adrenalectomy.

  20. Bleomycin-Induced Flagellate Erythema in a Patient Diagnosed with Ovarian Yolk Sac Tumor.

    PubMed

    Boussios, Stergios; Moschetta, Michele; McLachlan, Jennifer; Banerjee, Susana

    2015-01-01

    Flagellate linear hyperpigmentation can rarely be caused by the chemotherapy agent, bleomycin. Herein, we describe the case of a 20-year-old woman treated with bleomycin for an ovarian yolk sac tumor and review the prominent features of this form of dermatitis. PMID:26798532

  1. Macitentan (ACT-064992), a Tissue-Targeting Endothelin Receptor Antagonist, Enhances Therapeutic Efficacy of Paclitaxel by Modulating Survival Pathways in Orthotopic Models of Metastatic Human Ovarian Cancer12

    PubMed Central

    Kim, Sun-Jin; Kim, Jang Seong; Kim, Seung Wook; Brantley, Emily; Yun, Seok Joong; He, Junqin; Maya, Marva; Zhang, Fahao; Wu, Qiuyu; Lehembre, François; Regenass, Urs; Fidler, Isaiah J

    2011-01-01

    Potential treatments for ovarian cancers that have become resistant to standard chemotherapies include modulators of tumor cell survival, such as endothelin receptor (ETR) antagonist. We investigated the therapeutic efficacy of the dual ETR antagonist, macitentan, on human ovarian cancer cells, SKOV3ip1 and IGROV1, growing orthotopically in nude mice. Mice with established disease were treated with vehicle (control), paclitaxel (weekly, intraperitoneal injections), macitentan (daily oral administrations), or a combination of paclitaxel and macitentan. Treatment with paclitaxel decreased tumor weight and volume of ascites. Combination therapy with macitentan and paclitaxel reduced tumor incidence and further reduced tumor weight and volume of ascites when compared with paclitaxel alone. Macitentan alone occasionally reduced tumor weight but alone had no effect on tumor incidence or ascites. Immunohistochemical analyses revealed that treatment with macitentan and macitentan plus paclitaxel inhibited the phosphorylation of ETRs and suppressed the survival pathways of tumor cells by decreasing the levels of pVEGFR2, pAkt, and pMAPK. The dose of macitentan necessary for inhibition of phosphorylation correlated with the dose required to increase antitumor efficacy of paclitaxel. Treatment with macitentan enhanced the cytotoxicity mediated by paclitaxel as measured by the degree of apoptosis in tumor cells and tumor-associated endothelial cells. Collectively, these results show that administration of macitentan in combination with paclitaxel prevents the progression of ovarian cancer in the peritoneal cavity of nude mice in part by inhibiting survival pathways of both tumor cells and tumor-associated endothelial cells. PMID:21403842

  2. Epithelial-mesenchymal transition, the tumor microenvironment, and metastatic behavior of epithelial malignancies

    PubMed Central

    Talbot, Lindsay J; Bhattacharya, Syamal D; Kuo, Paul C

    2012-01-01

    Objective The mechanisms of cancer metastasis have been intensely studied recently and may provide vital therapeutic targets for metastasis prevention. We sought to review the contribution of epithelial-mesenchymal transition and the tumor microenvironment to cancer metastasis. Summary Background Data Epithelial-mesenchymal transition is the process by which epithelial cells lose cell-cell junctions and baso-apical polarity and acquire plasticity, mobility, invasive capacity, stemlike characteristics, and resistance to apoptosis. This cell biology program is active in embryology, wound healing, and pathologically in cancer metastasis, and along with the mechanical and cellular components of the tumor microenvironment, provides critical impetus for epithelial malignancies to acquire metastatic capability. Methods A literature review was performed using PubMed for “epithelial-mesenchymal transition”, “tumor microenvironment”, “TGF-β and cancer”, “Wnt and epithelial-mesenchymal transition”, “Notch and epithelial-mesenchymal transition”, “Hedgehog and epithelial-mesenchymal transition” and “hypoxia and metastasis”. Relevant primary studies and review articles were assessed. Results Major signaling pathways involved in epithelial-mesenchymal transition include TGF-β, Wnt, Notch, Hedgehog, and others. These pathways converge on several transcription factors, including zinc finger proteins Snail and Slug, Twist, ZEB 1/2, and Smads. These factors interact with one another and others to provide crosstalk between the relevant signaling pathways. MicroRNA suppression and epigenetic changes also influence the changes involved in epithelial-mesenchymal transition. Cellular and mechanical components of the tumor microenvironment are also critical in determining metastatic potential. Conclusions While the mechanisms promoting metastasis are extremely wide ranging and still under intense investigation, the epithelial-mesenchymal transition program and

  3. Heparan Sulfate Degradation: Relation to Tumor Invasive and Metastatic Properties of Mouse B16 Melanoma Sublines

    NASA Astrophysics Data System (ADS)

    Nakajima, Motowo; Irimura, Tatsuro; di Ferrante, Daniela; di Ferrante, Nicola; Nicolson, Garth L.

    1983-05-01

    After transport in the blood and implantation in the microcirculation, metastatic tumor cells must invade the vascular endothelium and underlying basal lamina. Mouse B16 melanoma sublines were used to determine the relation between metastatic properties and the ability of the sublines to degrade enzymatically the sulfated glycosaminoglycans present in the extracellular matrix of cultured vascular endothelial cells. Highly invasive and metastatic B16 sublines degraded matrix glycosaminoglycans faster than did sublines of lower metastatic potential. The main products of this matrix degradation were heparan sulfate fragments. Intact B16 cells (or their cell-free homogenates) with a high potential for lung colonization degraded purified heparan sulfate from bovine lung at higher rates than did B16 cells with a poor potential for lung colonization. Analysis of the degradation fragments indicated that B16 cells have a heparan sulfate endoglycosidase. Thus the abilities of B16 melanoma cells to extravasate and successfully colonize the lung may be related to their capacities to degrade heparan sulfate in the walls of pulmonary blood vessels.

  4. Photothermal and immunological reactions against metastatic tumors using laser photosensitizer immunoadjuvant

    NASA Astrophysics Data System (ADS)

    Chen, Wei R.; El-Samad, Ahmad; Nordquist, Robert E.

    1999-06-01

    Photothermal tissue interaction is the most common phenomenon when laser energy is deposited in tissue. Because of the sensitivity of cancer cells to temperature increase, photothermal reaction can be an effective mechanism of direct cancer destruction using lasers. Tumor-specific immune response is crucial in achieving systemic and long-term cures for cancers, particularly for metastatic cancers. Can photothermal interaction induce sufficient immunological reaction when the local destruction of tumor cells occurs? To achieve selective photothermal destruction, indocyanine green as a photosensitizer was directly injected into rat mammary tumors, followed by irradiation of 805 nm laser light. Although extensive photothermal tumor killing was achieved and tumor growth was slowed down immediately following the treatment, photothermal reaction alone was shown not sufficient in controlling the treated primary tumors and their metastases. When an immunoadjuvant was used with the indocyanine green, however, the same laser treatment not only could eventually eradicate the treated primary tumors but also eradicate the untreated metastases at remote sites. The tumor eradication went through a growth-regression process over a period of six to nine weeks post-treatment, indicating an induced immune response. The Western Blot analysis using the serum from a laser-immunotherapy cured rat showed that the tumor-specific antibody induced by the treatment had a long- lasting effect. Our experimental data indicated that photothermal interaction alone was not sufficient to slow and eventually reverse tumor growth. However, it can reduce the tumor burden and at the same time release tumor antigens to be recognized by the host immune system. Therefore, in conjunction with specific immunological stimulation using in situ immunoadjuvants, the selective thermal injury to tumors plays an important and a direct role in this laser immunotherapy.

  5. [Anesthetic Induction in a Patient with Giant Ovarian Tumor Who Developed Severe Hemodynamic Instability].

    PubMed

    Aoi, Ryota; Ishihara, Mariko; Soh, Mirei; Kohno, Michihiko; Soga, Mayumi; Kohata, Hisakazu; Takahashi, Kan

    2015-08-01

    A 45 year-old woman underwent a laparotomy for a giant ovarian tumor under general anesthesia. Preoperative CT scan revealed a 30 cm-diameter tumor compressing IVC. She had slight respiratory discomfort on supine position, but respiratory function test showed no abnormalities. In the operating room, after oxygenation for 3 minutes, general anesthesia was induced with fentanyl 100 μg, propofol 90 mg and rocuronium 40 mg on supine position. Immediately after the induction, her systolic blood pressure and heart rate fell to 45 mmHg and 40 beats per minute, respectively. We considered that her hemodynamic instability was supine hypotensive syndrome due to giant ovarian tumor. Therefore we placed her 30 degree right side up and pushed her tumor to the left so as not to compress the IVC. We rapidly injected acetated Ringer's solution 500 ml, ephedrine 12 mg and phenylephrine 0.1 mg, and her hemodynamic status soon recovered to normal ranges. The anesthetic induction of a patient with a giant ovarian tumor is challenging. Some reports recommend strategies such as induction on lateral position or suctioning tumor contents before induction. Careful induction of general anesthesia is required for these patients. PMID:26442415

  6. Human Ovarian Cancer Stroma Contains Luteinized Theca Cells Harboring Tumor Suppressor Gene GT198 Mutations*

    PubMed Central

    Peng, Min; Zhang, Hao; Jaafar, Lahcen; Risinger, John I.; Huang, Shuang; Mivechi, Nahid F.; Ko, Lan

    2013-01-01

    Ovarian cancer is a highly lethal gynecological cancer, and its causes remain to be understood. Using a recently identified tumor suppressor gene, GT198 (PSMC3IP), as a unique marker, we searched for the identity of GT198 mutant cells in ovarian cancer. GT198 has germ line mutations in familial and early onset breast and ovarian cancers and recurrent somatic mutations in sporadic fallopian tube cancers. GT198 protein has been shown as a steroid hormone receptor coregulator and also as a crucial factor in DNA repair. In this study, using GT198 as a marker for microdissection, we find that ovarian tumor stromal cells harboring GT198 mutations are present in various types of ovarian cancer including high and low grade serous, endometrioid, mucinous, clear cell, and granulosa cell carcinomas and in precursor lesions such as inclusion cysts. The mutant stromal cells consist of a luteinized theca cell lineage at various differentiation stages including CD133+, CD44+, and CD34+ cells, although the vast majority of them are differentiated overexpressing steroidogenic enzyme CYP17, a theca cell-specific marker. In addition, wild type GT198 suppresses whereas mutant GT198 protein stimulates CYP17 expression. The chromatin-bound GT198 on the human CYP17 promoter is decreased by overexpressing mutant GT198 protein, implicating the loss of wild type suppression in mutant cells. Together, our results suggest that GT198 mutant luteinized theca cells overexpressing CYP17 are common in ovarian cancer stroma. Because first hit cancer gene mutations would specifically mark cancer-inducing cells, the identification of mutant luteinized theca cells may add crucial evidence in understanding the cause of human ovarian cancer. PMID:24097974

  7. CSF1-ETS2-induced microRNA in myeloid cells promote metastatic tumor growth.

    PubMed

    Mathsyaraja, H; Thies, K; Taffany, D A; Deighan, C; Liu, T; Yu, L; Fernandez, S A; Shapiro, C; Otero, J; Timmers, C; Lustberg, M B; Chalmers, J; Leone, G; Ostrowski, M C

    2015-07-01

    Metastasis of solid tumors is associated with poor prognosis and bleak survival rates. Tumor-infiltrating myeloid cells (TIMs) are known to promote metastasis, but the mechanisms underlying their collaboration with tumor cells remain unknown. Here, we report an oncogenic role for microRNA (miR) in driving M2 reprogramming in TIMs, characterized by the acquisition of pro-tumor and pro-angiogenic properties. The expression of miR-21, miR-29a, miR-142-3p and miR-223 increased in myeloid cells during tumor progression in mouse models of breast cancer and melanoma metastasis. Further, we show that these miRs are regulated by the CSF1-ETS2 pathway in macrophages. A loss-of-function approach utilizing selective depletion of the miR-processing enzyme Dicer in mature myeloid cells blocks angiogenesis and metastatic tumor growth. Ectopic expression of miR-21 and miR-29a promotes angiogenesis and tumor cell proliferation through the downregulation of anti-angiogenic genes such as Col4a2, Spry1 and Timp3, whereas knockdown of the miRs impedes these processes. miR-21 and miR-29a are expressed in Csf1r+ myeloid cells associated with human metastatic breast cancer, and levels of these miRs in CD115+ non-classical monocytes correlates with metastatic tumor burden in patients. Taken together, our results suggest that miR-21 and miR-29a are essential for the pro-tumor functions of myeloid cells and the CSF1-ETS2 pathway upstream of the miRs serves as an attractive therapeutic target for the inhibition of M2 remodeling of macrophages during malignancy. In addition, miR-21 and miR-29a in circulating myeloid cells may potentially serve as biomarkers to measure therapeutic efficacy of targeted therapies for CSF1 signaling. PMID:25241894

  8. Gemcitabine Hydrochloride With or Without WEE1 Inhibitor MK-1775 in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2016-07-12

    Ovarian Brenner Tumor; Ovarian Carcinosarcoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Serous Surface Papillary Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Ovarian Carcinoma

  9. Integrated multimodal imaging of dynamic bone-tumor alterations associated with metastatic prostate cancer.

    PubMed

    Brisset, Jean-Christophe; Hoff, Benjamin A; Chenevert, Thomas L; Jacobson, Jon A; Boes, Jennifer L; Galbán, Stefanie; Rehemtulla, Alnawaz; Johnson, Timothy D; Pienta, Kenneth J; Galbán, Craig J; Meyer, Charles R; Schakel, Timothy; Nicolay, Klaas; Alva, Ajjai S; Hussain, Maha; Ross, Brian D

    2015-01-01

    Bone metastasis occurs for men with advanced prostate cancer which promotes osseous growth and destruction driven by alterations in osteoblast and osteoclast homeostasis. Patients can experience pain, spontaneous fractures and morbidity eroding overall quality of life. The complex and dynamic cellular interactions within the bone microenvironment limit current treatment options thus prostate to bone metastases remains incurable. This study uses voxel-based analysis of diffusion-weighted MRI and CT scans to simultaneously evaluate temporal changes in normal bone homeostasis along with prostate bone metatastsis to deliver an improved understanding of the spatiotemporal local microenvironment. Dynamic tumor-stromal interactions were assessed during treatment in mouse models along with a pilot prospective clinical trial with metastatic hormone sensitive and castration resistant prostate cancer patients with bone metastases. Longitudinal changes in tumor and bone imaging metrics during delivery of therapy were quantified. Studies revealed that voxel-based parametric response maps (PRM) of DW-MRI and CT scans could be used to quantify and spatially visualize dynamic changes during prostate tumor growth and in response to treatment thereby distinguishing patients with stable disease from those with progressive disease (p<0.05). These studies suggest that PRM imaging biomarkers are useful for detection of the impact of prostate tumor-stromal responses to therapies thus demonstrating the potential of multi-modal PRM image-based biomarkers as a novel means for assessing dynamic alterations associated with metastatic prostate cancer. These results establish an integrated and clinically translatable approach which can be readily implemented for improving the clinical management of patients with metastatic bone disease. PMID:25859981

  10. Integrated Multimodal Imaging of Dynamic Bone-Tumor Alterations Associated with Metastatic Prostate Cancer

    PubMed Central

    Chenevert, Thomas L.; Jacobson, Jon A.; Boes, Jennifer L.; Galbán, Stefanie; Rehemtulla, Alnawaz; Johnson, Timothy D.; Pienta, Kenneth J.; Galbán, Craig J.; Meyer, Charles R.; Schakel, Timothy; Nicolay, Klaas; Alva, Ajjai S.; Hussain, Maha; Ross, Brian D.

    2015-01-01

    Bone metastasis occurs for men with advanced prostate cancer which promotes osseous growth and destruction driven by alterations in osteoblast and osteoclast homeostasis. Patients can experience pain, spontaneous fractures and morbidity eroding overall quality of life. The complex and dynamic cellular interactions within the bone microenvironment limit current treatment options thus prostate to bone metastases remains incurable. This study uses voxel-based analysis of diffusion-weighted MRI and CT scans to simultaneously evaluate temporal changes in normal bone homeostasis along with prostate bone metatastsis to deliver an improved understanding of the spatiotemporal local microenvironment. Dynamic tumor-stromal interactions were assessed during treatment in mouse models along with a pilot prospective clinical trial with metastatic hormone sensitive and castration resistant prostate cancer patients with bone metastases. Longitudinal changes in tumor and bone imaging metrics during delivery of therapy were quantified. Studies revealed that voxel-based parametric response maps (PRM) of DW-MRI and CT scans could be used to quantify and spatially visualize dynamic changes during prostate tumor growth and in response to treatment thereby distinguishing patients with stable disease from those with progressive disease (p<0.05). These studies suggest that PRM imaging biomarkers are useful for detection of the impact of prostate tumor-stromal responses to therapies thus demonstrating the potential of multi-modal PRM image-based biomarkers as a novel means for assessing dynamic alterations associated with metastatic prostate cancer. These results establish an integrated and clinically translatable approach which can be readily implemented for improving the clinical management of patients with metastatic bone disease. Trial Registration ClinicalTrials.gov NCT02064283 PMID:25859981

  11. Novel Methylated Biomarkers and a Robust Assay to Detect Circulating Tumor DNA in Metastatic Breast Cancer

    PubMed Central

    Fackler, Mary Jo; Bujanda, Zoila Lopez; Umbricht, Christopher; Teo, Wei Wen; Cho, Soonweng; Zhang, Zhe; Visvanathan, Kala; Jeter, Stacie; Argani, Pedram; Wang, Chenguang; Lyman, Jaclyn P.; de Brot, Marina; Ingle, James N.; Boughey, Judy; McGuire, Kandace; King, Tari A.; Carey, Lisa A.; Cope, Leslie; Wolff, Antonio C.; Sukumar, Saraswati

    2015-01-01

    The ability to consistently detect cell-free tumor-specific DNA in peripheral blood of patients with metastatic breast cancer provides the opportunity to detect changes in tumor burden and to monitor response to treatment. We developed cMethDNA, a quantitative multiplexed methylation-specific PCR assay for a panel of ten genes, consisting of novel and known breast cancer hypermethylated markers identified by mining our previously reported study of DNA methylation patterns in breast tissue (103 cancer, 21 normal on the Illumina HumanMethylation27 Beadchip) and then validating the 10-gene panel in a TCGA breast cancer methylome database. For cMethDNA, a fixed physiological level (50 copies) of artificially constructed, standard non-human reference DNA specific for each gene is introduced into in a constant volume of serum (300 μl) prior to purification of the DNA, facilitating a sensitive, specific, robust and quantitative assay of tumor DNA, with broad dynamic range. Cancer-specific methylated DNA was detected in Training (28 normal, 24 cancer) and Test (27 normal, 33 cancer) sets of recurrent Stage 4 patient sera with a sensitivity of 91% and a specificity of 96% in the test set. In a pilot study, cMethDNA assay faithfully reflected patient response to chemotherapy (N = 29). A core methylation signature present in the primary breast cancer was retained in serum and metastatic tissues collected at autopsy 2–11 years after diagnosis of the disease. Together, our data suggest that the cMethDNA assay can detect advanced breast cancer, and monitor tumor burden and treatment response in women with metastatic breast cancer. PMID:24737128

  12. Isolation and Characterization of Circulating Tumor Cells from Patients with Localized and Metastatic Prostate Cancer

    PubMed Central

    Stott, Shannon L.; Lee, Richard J.; Nagrath, Sunitha; Yu, Min; Miyamoto, David T.; Ulkus, Lindsey; Inserra, Elizabeth J.; Ulman, Matthew; Springer, Simeon; Nakamura, Zev; Moore, Alessandra L.; Tsukrov, Dina I.; Kempner, Maria E.; Dahl, Douglas M.; Wu, Chin-Lee; Iafrate, A. John; Smith, Matthew R.; Tompkins, Ronald G.; Sequist, Lecia V.; Toner, Mehmet; Haber, Daniel A.; Maheswaran, Shyamala

    2011-01-01

    Rare circulating tumor cells (CTCs) are present in the blood of patients with metastatic epithelial cancers but have been difficult to measure routinely. We report a quantitative automated imaging system for analysis of prostate CTCs, taking advantage of prostate-specific antigen (PSA), a unique prostate tumor–associated marker. The specificity of PSA staining enabled optimization of criteria for baseline image intensity, morphometric measurements, and integration of multiple signals in a three-dimensional microfluidic device. In a pilot analysis, we detected CTCs in prostate cancer patients with localized disease, before surgical tumor removal in 8 of 19 (42%) patients (range, 38 to 222 CTCs per milliliter). For 6 of the 8 patients with preoperative CTCs, a precipitous postoperative decline (<24 hours) suggests a short half-life for CTCs in the blood circulation. Other patients had persistent CTCs for up to 3 months after prostate removal, suggesting early but transient disseminated tumor deposits. In patients with metastatic prostate cancer, CTCs were detected in 23 of 36 (64%) cases (range, 14 to 5000 CTCs per milliliter). In previously untreated patients followed longitudinally, the numbers of CTCs declined after the initiation of effective therapy. The prostate cancer–specific TMPRSS2-ERG fusion was detectable in RNA extracted from CTCs from 9 of 20 (45%) patients with metastatic disease, and dual staining of captured CTCs for PSA and the cell division marker Ki67 indicated a broad range for the proportion of proliferating cells among CTCs. This method for analysis of CTCs will facilitate the application of noninvasive tumor sampling to direct targeted therapies in advanced prostate cancer and warrants the initiation of long-term clinical studies to test the importance of CTCs in invasive localized disease. PMID:20424012

  13. Hepatic Arterial Chemoembolization Using Drug-Eluting Beads in Gastrointestinal Neuroendocrine Tumor Metastatic to the Liver

    SciTech Connect

    Gaur, Shantanu K.; Friese, Jeremy L.; Sadow, Cheryl A.; Ayyagari, Rajasekhara; Binkert, Christoph A.; Schenker, Matthew P.; Kulke, Matthew; Baum, Richard

    2011-06-15

    Purpose: This study was designed to evaluate short (<3 months) and intermediate-term (>3 months) follow-up in patients with metastatic neuroendocrine tumor to the liver who underwent hepatic arterial chemoembolization with drug-eluting beads at a single institution. Methods: Institutional review board approval was obtained for this retrospective review. All patients who were treated with 100-300 or 300-500 {mu}m drug-eluting LC Beads (Biocompatibles, UK) preloaded with doxorubicin (range, 50-100 mg) for GI neuroendocrine tumor metastatic to the liver from June 2004 to June 2009 were included. CT and MRI were evaluated for progression using Response Evaluation Criteria In Solid Tumors (RECIST) or European Association for the Study of the Liver (EASL) criteria. Short-term (<3 months) and intermediate-term (>3 months) imaging response was determined and Kaplan-Meier survival curves were plotted. Results: Thirty-eight drug-eluting bead chemoembolization procedures were performed on 32 hepatic lobes, comprising 21 treatment cycles in 18 patients. All procedures were technically successful with two major complications (biliary injuries). At short-term follow-up (<3 months), 22 of 38 (58%) procedures and 10 of 21 (48%) treatment cycles produced an objective response (OR) with the remainder having stable disease (SD). At intermediate-term follow-up (mean, 445 days; range, 163-1247), 17 of 26 (65%) procedures and 8 of 14 (57%) treatment cycles produced an OR. Probability of progressing was approximately 52% at 1 year with a median time to progression of 419 days. Conclusions: Drug-eluting bead chemoembolization is a reasonable alternative to hepatic arterial embolization and chemoembolization for the treatment of metastatic neuroendocrine tumor to the liver.

  14. S100P is a useful marker for differentiation of ovarian mucinous tumors.

    PubMed

    Umezaki, Y; Ito, M; Nakashima, M; Mihara, Y; Naruke, Y; Kurohama, H; Yatsunami, N; Yasuhi, I

    2015-01-01

    The S100P protein stimulates cell proliferation and survival, thereby contributing to tumor progression. The purpose of this study was to evaluate S100P expression in the three subtypes of mucinous cystic tumors, cystadenomas, borderline tumors, and adenocarcinomas. The authors examined nuclear S100P expression in 60 mucinous ovarian tumor specimens, including 24 specimens of mucinous cystadenoma, 15 of borderline tumors, and 21 of adenocarcinomas. Immunohistochemistry revealed S100P expression followed one of three patterns: (1) Expressed in most nuclei of mucinous epithelial cells, (2) sporadic (spotted or patchy) expression, or (3) absent or rarely expressed in the nuclei of mucinous epithelial cells. Most adenomas showed the first expression pattern, and borderline tumors often showed a patchy expression pattern. Adenocarcinomas generally demonstrated absence of S100P expression. These data suggest that S100P is a useful histological marker to differentiate between benign, borderline, and malignant mucinous tumors of the ovary. PMID:26050349

  15. A6 in Treating Patients With Persistent or Recurrent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2015-02-27

    Fallopian Tube Carcinoma; Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Primary Peritoneal Carcinoma; Recurrent Ovarian Carcinoma; Undifferentiated Ovarian Carcinoma

  16. [Methods and conditions of fertility preservation in early-stage ovarian tumors].

    PubMed

    Szatmári, Erzsébet; Máté, Szabolcs; Sipos, Norbert; Szánthó, András; Silhavy, Mihály; Rigó, János

    2013-04-01

    The aim of this study is to review the literature of fertility-sparing techniques and their safety in early-stage malignant ovarian tumors, especially in epithelial ovarian cancer. Fertility preservation is widely accepted in early-stage borderline, germ cell and sex cord-stromal tumors. Based on data from retrospective studies, fertility-sparing surgery in epithelial ovarian cancer can be recommended in stage IA, grade 1-2 and favorable hystologic type ovarian cancer. Above stage IA, or in grade 3, or in clear-cell tumors decision making process about fertility-sparing surgery should be individual. Correct surgical staging is mandatory and oncologic safety should be of primary importance. In the group of carefully selected patients oncological outcomes are identical to those of radical surgery. Spontaneous pregnancy rates vary, but they are generally high. Adequate counseling with patients, detailed documentation and careful follow-up is of outstanding importance. In order to improve the quality of fertility preservation techniques, establishment of treatment centers is recommended. PMID:23545230

  17. Talazoparib in Treating Patients With Advanced or Metastatic Solid Tumors That Cannot Be Removed by Surgery and Liver or Kidney Dysfunction

    ClinicalTrials.gov

    2016-04-05

    Estrogen Receptor Negative; Head and Neck Squamous Cell Carcinoma; HER2/Neu Negative; Hormone-Resistant Prostate Cancer; Metastatic Pancreatic Adenocarcinoma; Progesterone Receptor Negative; Solid Neoplasm; Stage III Mesothelioma; Stage IIIA Gastric Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Small Cell Lung Carcinoma; Stage IIIB Gastric Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Small Cell Lung Carcinoma; Stage IIIC Gastric Cancer; Stage IIIC Ovarian Cancer; Stage IV Mesothelioma; Stage IV Non-Small Cell Lung Cancer; Stage IV Ovarian Cancer; Stage IV Small Cell Lung Carcinoma; Triple-Negative Breast Carcinoma

  18. 7-Hydroxystaurosporine and Irinotecan Hydrochloride in Treating Patients With Metastatic or Unresectable Solid Tumors or Triple Negative Breast Cancer (Currently Accruing Only Triple-negative Breast Cancer Patients Since 6/8/2007)

    ClinicalTrials.gov

    2013-09-27

    Advanced Adult Primary Liver Cancer; Carcinoma of the Appendix; Estrogen Receptor-negative Breast Cancer; Extensive Stage Small Cell Lung Cancer; Gastrointestinal Stromal Tumor; HER2-negative Breast Cancer; Metastatic Gastrointestinal Carcinoid Tumor; Ovarian Sarcoma; Ovarian Stromal Cancer; Progesterone Receptor-negative Breast Cancer; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Adult Primary Liver Cancer; Recurrent Anal Cancer; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Borderline Ovarian Surface Epithelial-stromal Tumor; Recurrent Breast Cancer; Recurrent Cervical Cancer; Recurrent Colon Cancer; Recurrent Endometrial Carcinoma; Recurrent Esophageal Cancer; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Prostate Cancer; Recurrent Rectal Cancer; Recurrent Salivary Gland Cancer; Recurrent Small Cell Lung Cancer; Recurrent Small Intestine Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral

  19. Symptomatic Ovarian Steroid Cell Tumor not Otherwise Specified in a Post-Menopausal Woman.

    PubMed

    Sood, Neha; Desai, Kaniksha; Chindris, Ana-Maria; Lewis, Jason; Dinh, Tri A

    2016-06-28

    Steroid cell tumor not otherwise specified (NOS) is a rare subtype of sex cord stromal tumor of the ovary and contributes less than 0.1% of all ovarian neoplasms. The majority of tumors occur in pre-menopausal women (mean age: 43 years), in which 56-77% of patients present with virilization due to excess testosterone. An 80-year-old woman with worsening alopecia and excessive growth of coarse hair on abdomen and genital area was found to have elevated serum testosterone level (462 ng/mL). Radiologic studies were consistent with bilateral adrenal adenomas. Bilateral adrenal venous sampling ruled out the adrenal gland as origin of hormone secretion. A diagnostic and therapeutic bilateral salpingo-oophorectomy confirmed steroid cell tumor NOS of the left ovary. Post-operatively, the patient had complete resolution of her symptoms and normalization of testosterone level. Our case emphasizes the importance of a clinical suspicion for an occult testosterone secreting ovarian tumor in a symptomatic patient without obvious ovarian mass on imaging. PMID:27441075

  20. Symptomatic Ovarian Steroid Cell Tumor not Otherwise Specified in a Post-Menopausal Woman

    PubMed Central

    Sood, Neha; Desai, Kaniksha; Chindris, Ana-Maria; Lewis, Jason; Dinh, Tri A.

    2016-01-01

    Steroid cell tumor not otherwise specified (NOS) is a rare subtype of sex cord stromal tumor of the ovary and contributes less than 0.1% of all ovarian neoplasms. The majority of tumors occur in pre-menopausal women (mean age: 43 years), in which 56-77% of patients present with virilization due to excess testosterone. An 80-year-old woman with worsening alopecia and excessive growth of coarse hair on abdomen and genital area was found to have elevated serum testosterone level (462 ng/mL). Radiologic studies were consistent with bilateral adrenal adenomas. Bilateral adrenal venous sampling ruled out the adrenal gland as origin of hormone secretion. A diagnostic and therapeutic bilateral salpingo-oophorectomy confirmed steroid cell tumor NOS of the left ovary. Post-operatively, the patient had complete resolution of her symptoms and normalization of testosterone level. Our case emphasizes the importance of a clinical suspicion for an occult testosterone secreting ovarian tumor in a symptomatic patient without obvious ovarian mass on imaging. PMID:27441075

  1. Hypercalcemia from metastatic pancreatic neuroendocrine tumor secreting 1,25-dihydroxyvitamin D

    PubMed Central

    Zhu, Viola; de las Morenas, Antonio; Janicek, Milos

    2014-01-01

    Malignant hypercalcemia occurs in about 20-30% of patients with cancer, both solid tumors and hematologic malignancies. The secretion of parathyroid hormone-related protein (PTH-rP) is the most common cause and has been shown to be the etiology of hypercalcemia associated with neuroendocrine tumors. Here we report the case of a patient with metastatic pancreatic neuroendocrine tumor who developed hypercalcemia more than 4 years after the initial diagnosis as a result of secretion of 1,25-dihydroxyvitamin D, a mechanism only commonly seen in lymphomas. The successful control of the patient’s disease with capecitabine and temozolomide led to the alleviation of this paraneoplastic syndrome. PMID:25083313

  2. SKAP2 Promotes Podosome Formation to Facilitate Tumor-Associated Macrophage Infiltration and Metastatic Progression.

    PubMed

    Tanaka, Masamitsu; Shimamura, Shintaro; Kuriyama, Sei; Maeda, Daichi; Goto, Akiteru; Aiba, Namiko

    2016-01-15

    Tumor-associated macrophages (TAM) play complex and pivotal roles during cancer progression. A subset of metastasis-associated macrophages accumulates within metastatic sites to promote the invasion and growth of tumor cells. Src kinase-associated phosphoprotein 2 (SKAP2), a substrate of Src family kinases, is highly expressed in macrophages from various tumors, but its contribution to the tumor-promoting behavior of TAMs is unknown. Here, we report that SKAP2 regulates podosome formation in macrophages to promote tumor invasion and metastasis. SKAP2 physically interacted with Wiskott-Aldrich syndrome protein (WASP) and localized to podosomes, which were rarely observed in SKAP2-null macrophages. The invasion of peritoneal macrophages derived from SKAP2-null mice was significantly reduced compared with wild-type macrophages, but could be rescued by the restoration of functional SKAP2 containing an intact tyrosine phosphorylation site and the ability to interact with WASP. Furthermore, SKAP2-null mice inoculated with lung cancer cells exhibited markedly decreased lung metastases characterized by reduced macrophage infiltration compared with wild-type mice. Moreover, intravenously injected SKAP2-null macrophages failed to efficiently infiltrate established tumors and promote their growth. Taken together, these findings reveal a novel mechanism by which macrophages assemble the appropriate motile machinery to infiltrate tumors and promote disease progression, and implicate SKAP2 as an attractive candidate for therapeutically targeting TAMs. PMID:26577701

  3. Epidemiologic and molecular characteristics of borderline and malignant epithelial ovarian tumors

    NASA Astrophysics Data System (ADS)

    Bastos, Eugenia Maria Chaves De Moraes

    Data from the Cancer and Steroid Hormone Study, a multicenter, population-based, case-control study were used to identify risk factors for epithelial ovarian cancer according to tumor behavior, histologic types, as well as p53 expression. Cases were women between 20 to 54 years old diagnosed with epithelial ovarian cancer from 1980 to 1982. Controls were women selected by random digit dialing. Tumor samples were analyzed for p53 overexpression using immunohistochemistry. Case-case and case-control conditional logistic regression models matched on age and diagnosing centers were used to calculate odds ratios (OR's) and 95% confidence intervals (CI's) for borderline, malignant, mucinous, and nonmucinous tumors, and p53 positive and p53 negative cases. The OR's for high number of lifetime ovulatory cycles (376-533 compared with less than 234) were 3.1 (95% CI 1.6-6.1) for malignant and 1.4 (95% CI 0.5-3.7) for borderline cases. The high number of ovulatory cycles was also a strong risk factor among nonmucinous cases. OR's for current and recent ex-smokers compared with never smokers were 2.8 (95% CI 1.7-4.8) for mucinous and 0.9 (95% CI 0.7-1.1) for nonmucinous types. Infertility showed a positive association with borderline ovarian cancer. Family history of ovarian or breast cancer was positively associated with malignant and nonmucinous cases. Parity had an inverse association with malignant ovarian cancer cases. When cases were subdivided by p53 results, the OR for tobacco smoking and p53 positive ovarian cancer was elevated for mucinous (OR = 3.9; 95% CI 0.8-18) at localized stage. Alcohol use showed a positive association with p53 positive malignant cases at advanced stage (OR = 2.0; 95% CI 1.2-3.2) and with p53 positive nonmucinous cases at advanced stage (OR = 2.1; 95% CI 1.2-3.4). A positive association between high number of ovulatory cycles and p53 positive malignant cases was observed in cases with localized stage (OR = 6.6; 95% CI 1.0-45) and advanced

  4. Erlotinib Plus Carboplatin and Paclitaxel in Ovarian Carcinoma

    ClinicalTrials.gov

    2015-10-29

    Brenner Tumor; Fallopian Tube Cancer; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Stage III Ovarian Epithelial Cancer; Stage IV Ovarian Epithelial Cancer

  5. Interstitial laser irradiation of metastatic mammary tumors in combination with intratumoral injection of immunoadjuvant

    NASA Astrophysics Data System (ADS)

    Joshi, Chet; Jose, Jessnie; Figueroa, Daniel; Goddard, Jessica; Li, Xiaosong; Liu, Hong; Nordquist, Robert E.; Hode, Tomas; Chen, Wei R.

    2012-03-01

    Laser immunotherapy (LIT) was developed to treat metastatic cancers using a combination of laser irradiation and immunological stimulation. The original design of LIT employs a non-invasive, selective laser photothermal interaction, using an in situ light-absorbing dye. However, this non-invasive treatment mode faces challenges in treating deep, large tumors. Furthermore, it has difficulties in the cases of highly pigmented skin overlying target tumors. To overcome these limitations, interstitial laser immunotherapy (ILIT) was proposed. In ILIT, a cylindrical, side-fire fiber diffuser is placed inside the target tumor to induce thermal damage. To enhance the interstitial irradiation induced photothermal interaction, an immunological modifier, glycated chitosan (GC), is injected into the tumor after the laser treatment. In this study, a cylindrical diffuser with an active length of 1 cm was used to treat tumors of 1 to 1.5 cm in size. Different laser powers (1 to 3 watts) and different irradiation durations (10 to 30 minutes) were used to test the thermal effects of ILIT. Different doses of the GC (1.0%, 0.1 to 0.6 ml per rat) were used to determine the immunological effects of ILIT. Our results show that the animal survival depends on both laser dose and GC dose. A dose of 0.2 ml per tumor appeared to result in the highest survival rate under interstitial laser irradiation with 2.5 watts and 20 minutes. While the results in this study are not conclusive, they indicate that interstitial laser irradiation can be combined with immunotherapy to treat metastatic cancers. Furthermore, our results suggest that an optimal combination of laser dose and GC dose could be obtained for future clinical protocols using interstitial laser immunotherapy.

  6. Monocytes mediate metastatic breast tumor cell adhesion to endothelium under flow

    PubMed Central

    Evani, Shankar J.; Prabhu, Rajesh G.; Gnanaruban, V.; Finol, Ender A.; Ramasubramanian, Anand K.

    2013-01-01

    Endothelial adhesion is necessary for the hematogenous dissemination of tumor cells. However, the metastatic breast tumor cell MDA-MB-231 does not bind to the endothelium under physiological flow conditions, suggesting alternate mechanisms of adhesion. Since monocytes are highly represented in the tumor microenvironment, and also bind to endothelium during inflammation, we hypothesized that the monocytes assist in the arrest of MDA-MB-231 on the endothelium. Using in vitro models of the dynamic shear environment of the vasculature, we show that TNF-α-activated THP1/primary human monocytes and MDA-MB-231 cells form stable aggregates, and that the monocytes in these aggregates mediate the adhesion of otherwise nonadherent MDA-MB-231 cells to inflamed endothelium under flow (55±2.4 vs. 1.7±0.82 at a shear stress of 0.5 dyn/cm2, P<0.01). We also show that the hydrodynamic forces determine the size and orientation of aggregates adhered to the endothelium, and strongly favor the attachment of small aggregates with tumor cells downstream of flow (74–86% doublets at 0.5–2 dyn/cm2, P<0.01). The 5-fold up-regulation of ICAM-1 on TNF-α-activated MDA-MB-231 cells through the Nf-κB pathway was found to be critical in MDA-MB-231–monocyte aggregation and endothelial adhesion. Our results demonstrate that, under inflammatory conditions, monocytes may serve to disseminate tumor cells through circulation, and the tumor–monocyte–endothelial axis may represent a new therapeutic target to reduce cancer metastasis.—Evani, S. J., Prabhu, R. G., Gnanaruban, V., Finol, E. A., Ramasubramanian, A. K. Monocytes mediate metastatic breast tumor cell adhesion to endothelium under flow. PMID:23616566

  7. Endoglin targeting inhibits tumor angiogenesis and metastatic spread in breast cancer.

    PubMed

    Paauwe, M; Heijkants, R C; Oudt, C H; van Pelt, G W; Cui, C; Theuer, C P; Hardwick, J C H; Sier, C F M; Hawinkels, L J A C

    2016-08-01

    Endoglin, a transforming growth factor-β co-receptor, is highly expressed on angiogenic endothelial cells in solid tumors. Therefore, targeting endoglin is currently being explored in clinical trials for anti-angiogenic therapy. In this project, the redundancy between endoglin and vascular endothelial growth factor (VEGF) signaling in angiogenesis and the effects of targeting both pathways on breast cancer metastasis were explored. In patient samples, increased endoglin signaling after VEGF inhibition was observed. In vitro TRC105, an endoglin-neutralizing antibody, increased VEGF signaling in endothelial cells. Moreover, combined targeting of the endoglin and VEGF pathway, with the VEGF receptor kinase inhibitor SU5416, increased antiangiogenic effects in vitro and in a zebrafish angiogenesis model. Next, in a mouse model for invasive lobular breast cancer, the effects of TRC105 and SU5416 on tumor growth and metastasis were explored. Although TRC105 and SU5416 decreased tumor vascular density, tumor volume was unaffected. Strikingly, in mice treated with TRC105, or TRC105 and SU5416 combined, a strong inhibition in the number of metastases was seen. Moreover, upon resection of the primary tumor, strong inhibition of metastatic spread by TRC105 was observed in an adjuvant setting. To confirm these data, we assessed the effects of endoglin-Fc (an endoglin ligand trap) on metastasis formation. Similar to treatment with TRC105 in the resection model, endoglin-Fc-expressing tumors showed strong inhibition of distant metastases. These results show, for the first time, that targeting endoglin, either with neutralizing antibodies or a ligand trap, strongly inhibits metastatic spread of breast cancer in vivo. PMID:26804178

  8. A spontaneously occurring malignant ovarian Sertoli cell tumor in a young Sprague Dawley rat

    PubMed Central

    Kinoshita, Yuichi; Yoshizawa, Katsuhiko; Emoto, Yuko; Yuki, Michiko; Yuri, Takashi; Shikata, Nobuaki; Elmore, Susan A.; Tsubura, Airo

    2015-01-01

    Primary ovarian tumors are generally uncommon in rats used in toxicologic studies. A malignant Sertoli cell tumor was present in the ovary of a 19-week-old female Sprague Dawley rat. Macroscopically, the mass was white and firm, 10 × 13 × 17 mm in size, and located in the right ovary. Histopathologically, the mass was composed of nests of pleomorphic cells, which formed seminiferous-like tubules separated by a thin fibrovascular stroma. The tubules were lined by tumor cells, which had basally located nuclei and abundant eosinophilic and vacuolated cytoplasm. In some areas, the tumor cells were arranged in a retiform growth pattern, mimicking a rete testis/ovarii. Disseminated metastases to the surfaces of the mesentery, spleen and liver were also present. Immunohistochemically, many tumor cells were strongly positive for vimentin, estrogen receptor α and Ki 67. Some tumor cells were positive for pancytokeratin and inhibin α. These findings closely resemble those of an ovarian-derived human malignant Sertoli cell tumor. From our review of the literature, we believe this is the first report of a spontaneous malignant Sertoli cell tumor in the ovary of a young laboratory rat. This case might provide useful historical control information for rat toxicity studies. PMID:26989303

  9. Impact of Non-Pulmonary Visceral Metastases in the Prognosis and Practice of Metastatic Testicular Germ Cell Tumors

    PubMed Central

    Rossi, Lorena; Martignano, Filippo; Gallà, Valentina; Maugeri, Antonio; Schepisi, Giuseppe

    2016-01-01

    Non-pulmonary visceral metastases, in bones, brain and liver, represent nearly the 10% of metastatic sites of advanced germ cell tumors and are associated with poor prognosis. This review article summarizes major evidences on the impact of different visceral sites on the prognosis, treatment and clinical outcome of patients with germ cell tumors. The clinic-biological mechanisms by which these metastatic sites are associated with poor clinical outcome remain unclear. The multimodality treatment showed a potential better survival, in particular in patients with relapsed disease. Patients with advanced germ cell tumors with visceral metastases should be referred to centers with high expertise in the clinical management of such disease. PMID:27471579

  10. Impact of Non-Pulmonary Visceral Metastases in the Prognosis and Practice of Metastatic Testicular Germ Cell Tumors.

    PubMed

    Rossi, Lorena; Martignano, Filippo; Gallà, Valentina; Maugeri, Antonio; Schepisi, Giuseppe

    2016-04-15

    Non-pulmonary visceral metastases, in bones, brain and liver, represent nearly the 10% of metastatic sites of advanced germ cell tumors and are associated with poor prognosis. This review article summarizes major evidences on the impact of different visceral sites on the prognosis, treatment and clinical outcome of patients with germ cell tumors. The clinic-biological mechanisms by which these metastatic sites are associated with poor clinical outcome remain unclear. The multimodality treatment showed a potential better survival, in particular in patients with relapsed disease. Patients with advanced germ cell tumors with visceral metastases should be referred to centers with high expertise in the clinical management of such disease. PMID:27471579

  11. CGH analysis of secondary genetic changes in Ewing tumors: correlation with metastatic disease in a series of 43 cases.

    PubMed

    Brisset, S; Schleiermacher, G; Peter, M; Mairal, A; Oberlin, O; Delattre, O; Aurias, A

    2001-10-01

    The occurrence of secondary chromosome changes is frequent in Ewing tumors, in particular trisomies for chromosomes 8 and 12, and unbalanced (1;16) translocations leading to gains of 1q and losses of 16q. The prognostic value of these secondary aberrations has not been statistically demonstrated. We report here a CGH analysis of a series of 43 primary tumors corresponding to 21 localized and 22 metastatic tumors. For five of them, a sufficient amount of DNA for the CGH analysis was available from the frozen samples. For 19 samples, a preliminary step of DOP-PCR amplification of the DNA was necessary. For the last 19 tumors, DNA was obtained after DOP-PCR amplification of small amount of DNA contaminating the RNA. As a whole, the main chromosome imbalances previously described, such as trisomies for 1q, 8, and 12, were observed. It is noteworthy that the mean number of imbalances was more frequent in localized versus metastatic tumors. Gain of 1q was more frequent in metastatic than in localized tumors. Nevertheless, these two results do not reach statistical significance. Conversely, a statistically significant excess of copy number of chromosome 2 was observed in non-metastatic tumors, suggesting that this imbalance, which has never been previously reported, could be associated with more favorable tumor behavior. PMID:11672775

  12. Effects of dimethyltriazenes on in vitro Lewis lung carcinoma tumor lines with different metastatic capacity.

    PubMed

    Zupi, G; Corsi, A; Sacchi, A; Lassiani, L; Giraldi, T

    1984-01-01

    The effects of a selective antimetastatic agent: the aryldimethyltriazene derivative 1-p-(3,3-dimethyl-1-triazeno)benzoic acid potassium salt (DM-COOK) have been examined on two in vitro tumor cell lines derived from lung metastases of Lewis lung carcinoma. These stabilized in vitro tumor cell lines named C108 and BC215 have been reported to differ in their metastatic potential evaluated as lung colony forming ability and as the number of spontaneous metastases produced after intramuscular implant of tumor cells. The cytotoxic effect of DM-COOK in vitro was also compared with the one demonstrated by the structure-related compound 4-(3,3-dimethyl-1-triazeno)imidazole-5- carboxamide (DTIC) on the same variant lines. Survival curves show a different chemosensitivity of the two in vitro lines to the DM-COOK treatment, whereas no differences were detected between C108 and BC215 after exposure to DTIC. Moreover, DM-COOK and DTIC exhibit different trends of cell killing, implying different mechanisms of action for the two drugs. Results are discussed in view of the selective in vitro action of the aryldimethyltriazene derivative DM-COOK on cells which express a high metastatic potential. PMID:6480290

  13. Whole exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer

    PubMed Central

    Lohr, Jens G.; Adalsteinsson, Viktor A.; Cibulskis, Kristian; Choudhury, Atish D.; Rosenberg, Mara; Cruz-Gordillo, Peter; Francis, Joshua; Zhang, Cheng-Zhong; Shalek, Alex K.; Satija, Rahul; Trombetta, John T.; Lu, Diana; Tallapragada, Naren; Tahirova, Narmin; Kim, Sora; Blumenstiel, Brendan; Sougnez, Carrie; Lowe, Alarice; Wong, Bang; Auclair, Daniel; Van Allen, Eliezer M.; Nakabayashi, Mari; Lis, Rosina T.; Lee, Gwo-Shu M.; Li, Tiantian; Chabot, Matthew S.; Ly, Amy; Taplin, Mary-Ellen; Clancy, Thomas E.; Loda, Massimo; Regev, Aviv; Meyerson, Matthew; Hahn, William C.; Kantoff, Philip W.; Golub, Todd R.; Getz, Gad; Boehm, Jesse S.; Love, J. Christopher

    2014-01-01

    Comprehensive analyses of cancer genomes promise to inform prognoses and precise cancer treatments. A major barrier, however, is inaccessibility of metastatic tissue. A potential solution is to characterize circulating tumor cells (CTCs), but this requires overcoming the challenges of isolating rare cells and sequencing low-input material. Here we report an integrated process to isolate, qualify and sequence whole exomes of CTCs with high fidelity, using a census-based sequencing strategy. Power calculations suggest that mapping of >99.995% of the standard exome is possible in CTCs. We validated our process in two prostate cancer patients including one for whom we sequenced CTCs, a lymph node metastasis and nine cores of the primary tumor. Fifty-one of 73 CTC mutations (70%) were observed in matched tissue. Moreover, we identified 10 early-trunk and 56 metastatic-trunk mutations in the non-CTC tumor samples and found 90% and 73% of these, respectively, in CTC exomes. This study establishes a foundation for CTC genomics in the clinic. PMID:24752078

  14. Therapy of metastatic pancreatic neuroendocrine tumors (pNETs): recent insights and advances

    PubMed Central

    Ito, Tetsuhide; Igarashi, Hisato

    2013-01-01

    Neuroendocrine tumors (NETs) [carcinoids, pancreatic neuroendocrine tumors (pNETs)] are becoming an increasing clinical problem because not only are they increasing in frequency, but they can frequently present with advanced disease that requires diagnostic and treatment approaches different from those used in the neoplasms that most physicians are used to seeing and treating. In the past few years there have been numerous advances in all aspects of NETs including: an understanding of their unique pathogenesis; specific classification systems developed which have prognostic value; novel methods of tumor localization developed; and novel treatment approaches described. In patients with advanced metastatic disease these include the use of newer chemotherapeutic approaches, an increased understanding of the role of surgery and cytoreductive methods, the development of methods for targeted delivery of cytotoxic agents, and the development of targeted medical therapies (everolimus, sunitinib) based on an increased understanding of the disease biology. Although pNETs and gastrointestinal NETs share many features, recent studies show they differ in pathogenesis and in many aspects of diagnosis and treatment, including their responsiveness to different therapies. Because of limited space, this review will be limited to the advances made in the management and treatment of patients with advanced metastatic pNETs over the past 5 years. PMID:22886480

  15. Tumor morphological evolution: directed migration and gain and loss of the self-metastatic phenotype

    PubMed Central

    2010-01-01

    Background Aside from the stepwise genetic alterations known to underlie cancer cell creation, the microenvironment is known to profoundly influence subsequent tumor development, morphology and metastasis. Invasive cluster formation has been assumed to be dependent on directed migration and a heterogeneous environment - a conclusion derived from complex models of tumor-environment interaction. At the same time, these models have not included the prospect, now supported by a preponderance of evidence, that only a minority of cancer cells may have stem cell capacity. This proves to weigh heavily on the microenvironmental requirements for the display of characteristic tumor growth phenotypes. We show using agent-based modeling that some defining features of tumor growth ascribed to directed migration might also be realized under random migration, and discuss broader implications for cause-and-effect determination in general. Results Considering only the properties of random migration in tumors composed of stem cells and committed cells, we are able to recapitulate a characteristic clustering feature of invasive tumor growth, a property we attribute to "self-metastatic" growth. When the additional influence of directed migrations under chemotactic environments are considered, we find that tumor growth and invasive morphology are supported while the tumor is distant from the source, but are progressively discouraged as the tumor converges about that source. Conclusions We show that invasive clustering can derive from basic kinetic assumptions often neglected in more complex models. While higher-order mechanisms, e.g. directed migration upon chemotactic stimuli, may result in clustering growth morphologies, exclusive attributions of this phenotype to this or other structured microenvironments would be inappropriate, in light of our finding these features are observable in a homogeneous environment. Furthermore, directed migration will result in loss of the invasive

  16. Paired box gene 2 is associated with estrogen receptor α in ovarian serous tumors: Potential theory basis for targeted therapy

    PubMed Central

    Wang, Min; Ma, Haifen

    2016-01-01

    It has been suggested that Paired box gene (PAX)2 is activated by estradiol via estrogen receptor (ER)α in breast and endometrial cancer. The expression of PAX2 was restricted to ovarian serous tumors and only one case was positive in borderline mucinous tumor in our previous study. In the present study, immunohistochemistry was performed to assess the expression of ERα in 58 cases of ovarian serous tumors, including 30 serous cystadenomas, 16 borderline serous cystadenomas, 12 serous carcinomas and 67 cases of ovarian mucinous tumors, including 29 mucinous cystadenoma, 23 borderline mucinous cystadenoma and 15 mucinous carcinoma, which were the same specimens with detection of PAX2 expression. The results demonstrated that ERα was expressed in 10% (3/30) of serous cystadenomas, 62.5% (10/16) borderline serous cystadenomas and 66.7% (8/12) serous carcinomas. The expression of ERα in borderline serous cystadenomas and serous carcinomas were significantly higher compared with that in serous cystadenomas (P<0.01). ERα was detected in 3.4% (1/29) mucinous cystadenoma, 26.1% (6/23) borderline mucinous cystadenoma and only 6.7% (1/15) mucinous carcinoma. Furthermore, a scatter plot of the expression of PAX2 and ERα revealed a linear correlation between them in ovarian serous tumors (P<0.0001). With few positive results, no correlation was determined in ovarian mucinous tumors. It was demonstrated that PAX2 is associated with ERα in ovarian serous tumors, and this may become a potential theory basis for targeted therapy for ovarian serous tumors. Further research is required to determine how PAX2 and ERα work together, and the role of targeted therapy in ovarian serous tumors. PMID:27446571

  17. Haptoglobin and CCR2 receptor expression in ovarian cancer cells that were exposed to ascitic fluid: Exploring a new role of haptoglobin in the tumoral microenvironment

    PubMed Central

    Garibay-Cerdenares, OL; Hernández-Ramírez, VI; Osorio-Trujillo, JC; Gallardo-Rincón, D; Talamás-Rohana, P

    2015-01-01

    Haptoglobin (Hp) is an acute-phase protein that is produced by the liver to capture the iron that is present in the blood circulation, thus avoiding its accumulation in the blood. Moreover, Hp has been detected in a wide variety of tissues, in which it performs various functions. In addition, this protein is considered a potential biomarker in many diseases, such as cancer, including ovarian carcinoma; however, its participation in the cancerous processes has not yet been determined. The objective of this work was to demonstrate the expression of Hp and its receptor CCR2 in the ovarian cancer cells and its possible involvement in the process of cell migration through changes in the rearrangement of the actin cytoskeleton using western blot and wound-healing assays and confirming by confocal microscopy. Ovarian cancer cells express both Hp and its receptor CCR2 but only after exposure to ascitic fluid, inducing moderated cell migration. However, when the cells are exposed to exogenous Hp, the expression of CCR2 is induced together with drastic changes in the actin cytoskeleton rearrangement. At the same time, Hp induced cell migration in a much more efficient manner than did ascitic fluid. These effects were blocked when the CCR2 synthetic antagonist RS102895 was used to pretreat the cells. These results suggest that Hp-induced changes in the cell morphology, actin cytoskeleton structure, and migration ability of tumor cells, is possibly “preparing” these cells for the potential induction of the metastatic phenotype. PMID:26211665

  18. Haptoglobin and CCR2 receptor expression in ovarian cancer cells that were exposed to ascitic fluid: exploring a new role of haptoglobin in the tumoral microenvironment.

    PubMed

    Garibay-Cerdenares, O L; Hernández-Ramírez, V I; Osorio-Trujillo, J C; Gallardo-Rincón, D; Talamás-Rohana, P

    2015-01-01

    Haptoglobin (Hp) is an acute-phase protein that is produced by the liver to capture the iron that is present in the blood circulation, thus avoiding its accumulation in the blood. Moreover, Hp has been detected in a wide variety of tissues, in which it performs various functions. In addition, this protein is considered a potential biomarker in many diseases, such as cancer, including ovarian carcinoma; however, its participation in the cancerous processes has not yet been determined. The objective of this work was to demonstrate the expression of Hp and its receptor CCR2 in the ovarian cancer cells and its possible involvement in the process of cell migration through changes in the rearrangement of the actin cytoskeleton using western blot and wound-healing assays and confirming by confocal microscopy. Ovarian cancer cells express both Hp and its receptor CCR2 but only after exposure to ascitic fluid, inducing moderated cell migration. However, when the cells are exposed to exogenous Hp, the expression of CCR2 is induced together with drastic changes in the actin cytoskeleton rearrangement. At the same time, Hp induced cell migration in a much more efficient manner than did ascitic fluid. These effects were blocked when the CCR2 synthetic antagonist RS102895 was used to pretreat the cells. These results suggest that Hp-induced changes in the cell morphology, actin cytoskeleton structure, and migration ability of tumor cells, is possibly "preparing" these cells for the potential induction of the metastatic phenotype. PMID:26211665

  19. Ovarian masses revisited: radiologic and pathologic correlation.

    PubMed

    Sutton, C L; McKinney, C D; Jones, J E; Gay, S B

    1992-09-01

    Diagnosis of ovarian masses can be difficult because many pathologic conditions can affect the ovary and have similar clinical and radiologic manifestations. Knowledge of pathologic, age-specific characteristics can help refine the differential diagnosis. Ovarian masses are nonneoplastic (ovarian functional cysts, polycystic ovary disease, and ovarian torsion) or neoplastic (surface epithelial, sex cord-stromal, germ cell, and metastatic tumors). Functional cysts, if complicated by hemorrhage, can have a confusing ultrasonographic (US) appearance. Polycystic disease and torsion are easily diagnosed with US. Benign and malignant forms of serous and mucinous surface epithelial tumors can usually be differentiated with US. Imaging features of surface epithelial tumors of low malignant potential are nonspecific, resembling those of benign serous and mucinous tumors. Mature (benign) teratomas are usually cystic, with components of fat, soft tissue, and calcium, and are sonographically distinct from immature (malignant) teratomas, which are mostly solid. Sex cord-stromal tumors occur more often in menopausal or postmenopausal women and are typically solid. Metastatic disease is less common than other ovarian tumors; however, its radiologic appearance may resemble those of other masses. PMID:1529129

  20. [Management of complications after residual tumor resection for metastatic testicular cancer].

    PubMed

    Lusch, A; Zaum, M; Winter, C; Albers, P

    2014-07-01

    Residual tumor resection (RTR) in patients with metastatic testicular cancer plays a pivotal role in a multimodal treatment. It can be performed unilaterally or as an extended bilateral RTR. Additional surgical procedures might be necessary, such as nephrectomy, splenectomy, partial colectomy, or vascular interventions with possible caval resection, cavotomy, or aortic resection with aortic grafting. Consequently, several complications can be seen in the intra- and postoperative course, most common of which are superficial wound infections, intestinal paralysis, lymphocele, and chylous ascites. We sought to describe complication management and how to prevent complications before they arise. PMID:25023235

  1. Neuroblastoma-targeted nanocarriers improve drug delivery and penetration, delay tumor growth and abrogate metastatic diffusion.

    PubMed

    Cossu, Irene; Bottoni, Gianluca; Loi, Monica; Emionite, Laura; Bartolini, Alice; Di Paolo, Daniela; Brignole, Chiara; Piaggio, Francesca; Perri, Patrizia; Sacchi, Angelina; Curnis, Flavio; Gagliani, Maria Cristina; Bruno, Silvia; Marini, Cecilia; Gori, Alessandro; Longhi, Renato; Murgia, Daniele; Sementa, Angela Rita; Cilli, Michele; Tacchetti, Carlo; Corti, Angelo; Sambuceti, Gianmario; Marchiò, Serena; Ponzoni, Mirco; Pastorino, Fabio

    2015-11-01

    Selective tumor targeting is expected to enhance drug delivery and to decrease toxicity, resulting in an improved therapeutic index. We have recently identified the HSYWLRS peptide sequence as a specific ligand for aggressive neuroblastoma, a childhood tumor mostly refractory to current therapies. Here we validated the specific binding of HSYWLRS to neuroblastoma cell suspensions obtained either from cell lines, animal models, or Schwannian-stroma poor, stage IV neuroblastoma patients. Binding of the biotinylated peptide and of HSYWLRS-functionalized fluorescent quantum dots or liposomal nanoparticles was dose-dependent and inhibited by an excess of free peptide. In animal models obtained by the orthotopic implant of either MYCN-amplified or MYCN single copy human neuroblastoma cell lines, treatment with HSYWLRS-targeted, doxorubicin-loaded Stealth Liposomes increased tumor vascular permeability and perfusion, enhancing tumor penetration of the drug. This formulation proved to exert a potent antitumor efficacy, as evaluated by bioluminescence imaging and micro-PET, leading to (i) delay of tumor growth paralleled by decreased tumor glucose consumption, and (ii) abrogation of metastatic spreading, accompanied by absence of systemic toxicity and significant increase in the animal life span. Our findings are functional to the design of targeted nanocarriers with potentiated therapeutic efficacy towards the clinical translation. PMID:26276694

  2. Circulating Tumor Cells in Metastatic Breast Cancer: A Prognostic and Predictive Marker

    PubMed Central

    Moussavi-Harami, Sayyed Farshid; Wisinski, Kari B.; Beebe, David J.

    2014-01-01

    The role of circulating tumor cells (CTCs) as a marker for disease progression in metastatic cancer is controversial. The current review will serve to summarize the evidence on CTCs as a marker of disease progression in patients with metastatic breast cancer. The immunohistochemistry(IHC)-based CellSearch® is the only FDA-approved isolation technique for quantifying CTCs in patients with metastatic breast cancer. We searched PubMed and Web of Knowledge for clinical studies that assessed the prognostic and predictive value of CTCs using IHC-based isolation. The patient outcomes reported include median and Cox-proportional hazard ratios for overall-survival (OS) and progression-free-survival (PFS). All studies reported shorter OS for CTC-positive patients versus CTC-negative. A subset of the selected trials reported significant lower median PFS for CTC-positive patients. The reported trials support the utility of CTC enumeration for patient prognosis. But further studies are required to determine the utility of CTC enumeration for guiding patient therapy. There are three clinical trials ongoing to test this hypothesis. These studies, and others, will further establish the role of CTCs in clinical practice. PMID:25914894

  3. Mucinous borderline ovarian tumors: Analysis of 75 patients from a single center

    PubMed Central

    Cömert, Duygu Kavak; Üreyen, Işın; Karalok, Alper; Taşçı, Tolga; Türkmen, Osman; Öcalan, Reyhan; Turan, Taner; Tulunay, Gökhan

    2016-01-01

    Objective To analyze the clinicopathologic features, recurrence and survival rates, reproductive history, and treatment of patients with mucinous borderline ovarian tumors (mBOTs). Material and Methods Patients with a diagnosis of mBOT were evaluated retrospectively. Patients with borderline ovarian tumors other than mucinous type and concomitant invasive cancer were excluded. Results A total of 75 patients were identified. Median age was 38 years. The most common symptom was pain (42.7%). Median CA-125 level was 23.5 IU/mL (range, 1–809 IU/mL). Median tumor size was 200 mm (range, 40–400 mm), and 6.7% of mBOTs were bilateral. Thirty-six (48%) patients underwent staging surgery. Two patients (5.9%) had nodal involvement. One patient received platinum-based adjuvant chemotherapy. One (1.3%) patient had recurrence. None of the patients died because of the ovarian tumor. A total of 43 patients had conservative surgery. Conclusion Prognosis of mBOTs is excellent, and fertility-sparing surgery should be considered in the reproductive age group. Furthermore, the necessity of staging surgery is controversial. PMID:27403076

  4. Unique proteome signature of post-chemotherapy ovarian cancer ascites-derived tumor cells.

    PubMed

    Ahmed, Nuzhat; Greening, David; Samardzija, Chantel; Escalona, Ruth M; Chen, Maoshan; Findlay, Jock K; Kannourakis, George

    2016-01-01

    Eighty % of ovarian cancer patients diagnosed at an advanced-stage have complete remission after initial surgery and chemotherapy. However, most patients die within <5 years due to episodes of recurrences resulting from the growth of residual chemoresistant cells. In an effort to identify mechanisms associated with chemoresistance and recurrence, we compared the expression of proteins in ascites-derived tumor cells isolated from advanced-stage ovarian cancer patients obtained at diagnosis (chemonaive, CN) and after chemotherapy treatments (chemoresistant/at recurrence, CR) by using in-depth, high-resolution label-free quantitative proteomic profiling. A total of 2,999 proteins were identified. Using a stringent selection criterion to define only significantly differentially expressed proteins, we report identification of 353 proteins. There were significant differences in proteins encoding for immune surveillance, DNA repair mechanisms, cytoskeleton rearrangement, cell-cell adhesion, cell cycle pathways, cellular transport, and proteins involved with glycine/proline/arginine synthesis in tumor cells isolated from CR relative to CN patients. Pathway analyses revealed enrichment of metabolic pathways, DNA repair mechanisms and energy metabolism pathways in CR tumor cells. In conclusion, this is the first proteomics study to comprehensively analyze ascites-derived tumor cells from CN and CR ovarian cancer patients. PMID:27470985

  5. Unique proteome signature of post-chemotherapy ovarian cancer ascites-derived tumor cells

    PubMed Central

    Ahmed, Nuzhat; Greening, David; Samardzija, Chantel; Escalona, Ruth M.; Chen, Maoshan; Findlay, Jock K.; Kannourakis, George

    2016-01-01

    Eighty % of ovarian cancer patients diagnosed at an advanced-stage have complete remission after initial surgery and chemotherapy. However, most patients die within <5 years due to episodes of recurrences resulting from the growth of residual chemoresistant cells. In an effort to identify mechanisms associated with chemoresistance and recurrence, we compared the expression of proteins in ascites-derived tumor cells isolated from advanced-stage ovarian cancer patients obtained at diagnosis (chemonaive, CN) and after chemotherapy treatments (chemoresistant/at recurrence, CR) by using in-depth, high-resolution label-free quantitative proteomic profiling. A total of 2,999 proteins were identified. Using a stringent selection criterion to define only significantly differentially expressed proteins, we report identification of 353 proteins. There were significant differences in proteins encoding for immune surveillance, DNA repair mechanisms, cytoskeleton rearrangement, cell-cell adhesion, cell cycle pathways, cellular transport, and proteins involved with glycine/proline/arginine synthesis in tumor cells isolated from CR relative to CN patients. Pathway analyses revealed enrichment of metabolic pathways, DNA repair mechanisms and energy metabolism pathways in CR tumor cells. In conclusion, this is the first proteomics study to comprehensively analyze ascites-derived tumor cells from CN and CR ovarian cancer patients. PMID:27470985

  6. Treatment response to transcatheter arterial embolization and chemoembolization in primary and metastatic tumors of the liver

    PubMed Central

    Artinyan, Avo; Nelson, Rebecca; Soriano, Perry; Chung, Vincent; Retseck, Janet; Reynolds, Jonathon; Marx, Howard; Kim, Joseph

    2008-01-01

    Introduction. Transcatheter arterial embolization (TAE) and chemoembolization (TACE) are increasingly used to treat unresectable primary and metastatic liver tumors. The purpose of this study was to determine the objective response to TAE and TACE in unresectable hepatic malignancies and to identify clinicopathologic predictors of response. Materials and methods. Seventy-nine consecutive patients who underwent 119 TAE/TACE procedures between 1998 and 2006 were reviewed. The change in maximal diameter of 121 evaluable lesions in 56 patients was calculated from pre and post-procedure imaging. Response rates were determined using Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. The Kaplan-Meier method was used to compare survival in responders vs. non-responders and in primary vs. metastatic histologies. Results. TAE and TACE resulted in a mean decrease in lesion size of 10.3%±1.9% (p<0.001). TACE (vs. TAE) and carcinoid tumors were associated with a greater response (p<0.05). Lesion response was not predicted by pre-treatment size, vascularity, or histology. The RECIST partial response (PR) rate was 12.3% and all partial responders were in the TACE group. Neuroendocrine tumors, and specifically carcinoid lesions, had a significantly greater PR rate (p<0.05). Overall survival, however, was not associated with histology or radiologic response. Discussion. TAE and TACE produce a significant objective treatment response by RECIST criteria. Response is greatest in neuroendocrine tumors and is independent of vascularity and lesion size. TACE appears to be superior to TAE. Although an association of response with improved survival was not demonstrated, large cohort studies are necessary to further define this relationship. PMID:19088924

  7. Phase II clinical trial of pasireotide long-acting repeatable in patients with metastatic neuroendocrine tumors

    PubMed Central

    Cives, M; Kunz, P L; Morse, B; Coppola, D; Schell, M J; Campos, T; Nguyen, P T; Nandoskar, P; Khandelwal, V; Strosberg, J R

    2015-01-01

    Pasireotide long-acting repeatable (LAR) is a novel somatostatin analog (SSA) with avid binding affinity to somatostatin receptor subtypes 1, 2, 3 (SSTR1,2,3) and 5 (SSTR5). Results from preclinical studies indicate that pasireotide can inhibit neuroendocrine tumor (NET) growth more robustly than octreotide in vitro. This open-label, phase II study assessed the clinical activity of pasireotide in treatment-naïve patients with metastatic grade 1 or 2 NETs. Patients with metastatic pancreatic and extra-pancreatic NETs were treated with pasireotide LAR (60 mg every 4 weeks). Previous systemic therapy, including octreotide and lanreotide, was not permitted. Tumor assessments were performed every 3 months using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), overall radiographic response rate (ORR), and safety. Twenty-nine patients were treated with pasireotide LAR (60 mg every 4 weeks) and 28 were evaluable for response. The median PFS was 11 months. The most favorable effect was observed in patients with low hepatic tumor burden, normal baseline chromogranin A, and high tumoral SSTR5 expression. Median OS has not been reached; the 30-month OS rate was 70%. The best radiographic response was partial response in one patient (4%), stable disease in 17 patients (60%), and progressive disease in ten patients (36%). Although grade 3/4 toxicities were rare, pasireotide LAR treatment was associated with a 79% rate of hyperglycemia including 14% grade 3 hyperglycemia. Although pasireotide appears to be an effective antiproliferative agent in the treatment of advanced NETs, the high incidence of hyperglycemia raises concerns regarding its suitability as a first-line systemic agent in unselected patients. SSTR5 expression is a potentially predictive biomarker for response. PMID:25376618

  8. Sulforaphane reduces molecular response to hypoxia in ovarian tumor cells independently of their resistance to chemotherapy

    PubMed Central

    PASTOREK, MICHAL; SIMKO, VERONIKA; TAKACOVA, MARTINA; BARATHOVA, MONIKA; BARTOSOVA, MARIA; HUNAKOVA, LUBA; SEDLAKOVA, OLGA; HUDECOVA, SONA; KRIZANOVA, OLGA; DEQUIEDT, FRANCK; PASTOREKOVA, SILVIA; SEDLAK, JAN

    2015-01-01

    One of the recently emerging anticancer strategies is the use of natural dietary compounds, such as sulforaphane, a cancer-chemopreventive isothiocyanate found in broccoli. Based on the growing evidence, sulforaphane acts through molecular mechanisms that interfere with multiple oncogenic pathways in diverse tumor cell types. Herein, we investigated the anticancer effects of bioavailable concentrations of sulforaphane in ovarian carcinoma cell line A2780 and its two derivatives, adriamycin-resistant A2780/ADR and cisplatin-resistant A2780/CP cell lines. Since tumor microenvironment is characterized by reduced oxygenation that induces aggressive tumor phenotype (such as increased invasiveness and resistance to chemotherapy), we evaluated the effects of sulforaphane in ovarian cancer cells exposed to hypoxia (2% O2). Using the cell-based reporter assay, we identified several oncogenic pathways modulated by sulforaphane in hypoxia by activating anticancer responses (p53, ARE, IRF-1, Pax-6 and XRE) and suppressing responses supporting tumor progression (AP-1 and HIF-1). We further showed that sulforaphane decreases the level of HIF-1α protein without affecting its transcription and stability. It can also diminish transcription and protein level of the HIF-1 target, CA IX, which protects tumor cells from hypoxia-induced pH imbalance and facilitates their migration/invasion. Accordingly, sulforaphane treatment leads to diminished pH regulation and reduced migration of ovarian carcinoma cells. These effects occur in all three ovarian cell lines suggesting that sulforaphane can overcome the chemoresistance of cancer cells. This offers a path potentially exploitable in sensitizing resistant cancer cells to therapy, and opens a window for the combined treatments of sulforaphane either with conventional chemotherapy, natural compounds, or with other small molecules. PMID:25955133

  9. [An analysis of 117 cases of patients who died from tumor recurrence or from the progression of ovarian malignancies].

    PubMed

    Kano, T; Sakakibara, K; Kamiya, N; Mizuno, K; Miyazaki, T; Ohta, M; Tomoda, Y

    1987-10-01

    Out of 403 patients with ovarian with malignancies during 1978 to, 1985, 117 (29.0%) died from the progression of a non-curative cancer (56 cases, 47.9%) or from a cancer recurrence (61 cases, 52.1%). The mean survival rate 117 cases was 13.4 months, of which 103 (88.0%) cases concerned patients who died within 2 years and 114 (97.4%) who died within 3 years. A histological analysis revealed that patients with a serous or an endometrial cancer had a longer survival rate than others. Among 61 recurrent cases, 59 (96.7%) fell into recurrence within 2 years. Regarding the relationship between a recurrent of cancer and its prognosis, patients with a recurrence of an ascitic or a metastatic disease had a poorer prognosis than patients with a pelvic or an abdominal mass. An aggressive operation, such as a resection of a recurrent tumor, even if small in volume, led to a better prognostic result than no therapy. PMID:3694804

  10. Tumor lysis syndrome in metastatic breast cancer after a single dose of paclitaxel.

    PubMed

    Vaidya, Gaurang Nandkishor; Acevedo, Russell

    2015-02-01

    Tumor lysis syndrome (TLS) is an oncologic emergency characterized by spillage of intracellular material into the blood caused by disruption of massive load of tumor cells. It is more commonly reported in hematological cancers and can have fatal consequences due to renal and multi-organ failure and arrhythmias due to electrolyte imbalance. We describe a case with metastatic breast cancer who presented with TLS after a single dose of paclitaxel, second such case in literature. The development of a risk stratification score to assess the need for hospitalization or close observation of these patients and the documentation of appropriate preventive strategies could help prevent such fatal occurrences. TLS should be included in the differential when cancer patients on treatment present with acute decompensation. PMID:25178848

  11. Graft versus tumor effect in the brain of a child with recurrent metastatic medulloblastoma.

    PubMed

    Abdel-Azim, Hisham; Kapoor, Neena; Mahadeo, Kris M; Finlay, Jonathan L

    2015-09-01

    Marrow ablative chemotherapy (MAC) with autologous hematopoietic stem cell transplantation (HSCT) is limited by poor bone marrow reserve after chemotherapy and/or radiotherapy, and the extent of bone/bone marrow disease. We report a child with recurrent metastatic medulloblastoma who received an allogeneic HSCT while in relapse and subsequently achieved radiological resolution of disease and favorable marrow minimal residual disease (MRD) response. Disease recurred intra-cranially at 304 days post-HSCT. Tumor biopsy 488 days post-HSCT showed infiltration with donor lymphocytes demonstrating graft-versus-tumor (GVT) effect. The patient remained alive >2 years post-HSCT. Allogeneic HSCT may be a consideration for high-risk recurrent medulloblastoma. PMID:25894457

  12. Tubo-ovarian abscess presenting as an ovarian tumor in a virginal adolescent: a case report.

    PubMed

    Sakar, M N; Gul, T; Atay, A E

    2012-01-01

    Tubo-ovarian abscess (TOA), a serious complication of pelvic inflammatory disease, unites the fallopian tube and ovary and, is rarely observed in sexually inactive adolescent girls. A pelvic mass, supposedly originating from the ovary, was detected in a 13-year-old sexually inactive girl suffering from abdominal pain and menstrual disorder. Pelvic ultrasonography pointed out a semisolid, hyperechogenic mass of 57x73 mm in the left adnexal area. Laparotomy revealed an unilateral TOA adhering to the bowel and omentum. Abscess drainage and adhesiolysis were performed and postoperative antibiotherapy was administered. TOA should be considered in the differential diagnosis of females with abdominal pain and adnexal mass whether sexual activity is present or not. PMID:23157053

  13. Rare Skin Adnexal and Melanocytic Tumors Arising in Ovarian Mature Cystic Teratomas: A Report of 3 Cases and Review of the Literature.

    PubMed

    Moulla, Alexandra A; Magdy, Nesreen; Francis, Nicholas; Taube, Janis; Ronnett, Brigitte M; El-Bahrawy, Mona

    2016-09-01

    Mature teratoma of the ovary is the most common primary ovarian tumor accounting for 15% (10%-20%) of all ovarian neoplasms. Skin and skin adnexal structures are the most common elements identified in mature teratomas. Benign and malignant skin tumors can arise in ovarian teratomas, the most common being epithelial tumors. Melanocytic and adnexal tumors developing in a teratoma are rare and can be easily overlooked. We report 3 cases and review melanocytic and skin adnexal tumors encountered in ovarian teratomas. PMID:26974995

  14. Advances in Personalized Targeted Treatment of Metastatic Melanoma and Non-Invasive Tumor Monitoring

    PubMed Central

    Klinac, Dragana; Gray, Elin S.; Millward, Michael; Ziman, Mel

    2013-01-01

    Despite extensive scientific progress in the melanoma field, treatment of advanced stage melanoma with chemotherapeutics and biotherapeutics has rarely provided response rates higher than 20%. In the past decade, targeted inhibitors have been developed for metastatic melanoma, leading to the advent of more personalized therapies of genetically characterized tumors. Here we review current melanoma treatments and emerging targeted molecular therapies. In particular we discuss the mutant BRAF inhibitors Vemurafenib and Dabrafenib, which markedly inhibit tumor growth and advance patients’ overall survival. However this response is almost inevitably followed by complete tumor relapse due to drug resistance hampering the encouraging initial responses. Several mechanisms of resistance within and outside the MAPK pathway have now been uncovered and have paved the way for clinical trials of combination therapies to try and overcome tumor relapse. It is apparent that personalized treatment management will be required in this new era of targeted treatment. Circulating tumor cells (CTCs) provide an easily accessible means of monitoring patient relapse and several new approaches are available for the molecular characterization of CTCs. Thus CTCs provide a monitoring tool to evaluate treatment efficacy and early detection of drug resistance in real time. We detail here how advances in the molecular analysis of CTCs may provide insight into new avenues of approaching therapeutic options that would benefit personalized melanoma management. PMID:23515890

  15. Deficiency for endoglin in tumor vasculature weakens the endothelial barrier to metastatic dissemination

    PubMed Central

    Anderberg, Charlotte; Cunha, Sara I.; Zhai, Zhenhua; Cortez, Eliane; Pardali, Evangelia; Johnson, Jill R.; Franco, Marcela; Páez-Ribes, Marta; Cordiner, Ross; Fuxe, Jonas; Johansson, Bengt R.; Goumans, Marie-José; Casanovas, Oriol; ten Dijke, Peter; Arthur, Helen M.

    2013-01-01

    Therapy-induced resistance remains a significant hurdle to achieve long-lasting responses and cures in cancer patients. We investigated the long-term consequences of genetically impaired angiogenesis by engineering multiple tumor models deprived of endoglin, a co-receptor for TGF-β in endothelial cells actively engaged in angiogenesis. Tumors from endoglin-deficient mice adapted to the weakened angiogenic response, and refractoriness to diminished endoglin signaling was accompanied by increased metastatic capability. Mechanistic studies in multiple mouse models of cancer revealed that deficiency for endoglin resulted in a tumor vasculature that displayed hallmarks of endothelial-to-mesenchymal transition, a process of previously unknown significance in cancer biology, but shown by us to be associated with a reduced capacity of the vasculature to avert tumor cell intra- and extravasation. Nevertheless, tumors deprived of endoglin exhibited a delayed onset of resistance to anti-VEGF (vascular endothelial growth factor) agents, illustrating the therapeutic utility of combinatorial targeting of multiple angiogenic pathways for the treatment of cancer. PMID:23401487

  16. KRAS Genotypic Changes of Circulating Tumor Cells during Treatment of Patients with Metastatic Colorectal Cancer

    PubMed Central

    Kalikaki, Aristea; Politaki, Helen; Souglakos, John; Apostolaki, Stella; Papadimitraki, Elisavet; Georgoulia, Nefeli; Tzardi, Maria; Mavroudis, Dimitris; Georgoulias, Vassilis; Voutsina, Alexandra

    2014-01-01

    Introduction Circulating tumor cells (CTCs) could represent a non-invasive source of cancer cells used for longitudinal monitoring of the tumoral mutation status throughout the course of the disease. The aims of the present study were to investigate the detection of KRAS mutations in CTCs from patients with metastatic colorectal cancer (mCRC) and to compare their mutation status during treatment or disease progression with that of the corresponding primary tumors. Materials and Methods Identification of the seven most common KRAS mutations on codons 12 and 13 was performed by Peptide Nucleic Acid (PNA)-based qPCR method. The sensitivity of the assay was determined after isolation of KRAS mutant cancer cells spiked into healthy donors' blood, using the CellSearch Epithelial Cell kit. Consistent detection of KRAS mutations was achieved in samples containing at least 10 tumor cells/7.5 ml of blood. Results The clinical utility of the assay was assessed in 48 blood samples drawn from 31 patients with mCRC. All patients had PIK3CA and BRAF wild type primary tumors and 14 KRAS mutant tumors. CTCs were detected in 65% of specimens obtained from 74% of patients. KRAS mutation analysis in CTC-enriched specimens showed that 45% and 16.7% of patients with mutant and wild type primary tumors, respectively, had detectable mutations in their CTCs. Assessing KRAS mutations in serial blood samples revealed that individual patient's CTCs exhibited different mutational status of KRAS during treatment. Conclusions The current findings support the rationale for using the CTCs as a dynamic source of tumor cells which, by re-evaluating their KRAS mutation status, could predict, perhaps more accurately, the response of mCRC patients to targeted therapy. PMID:25137394

  17. Fine-needle aspiration cytology of ovarian steroid cell tumor: A rare case report.

    PubMed

    Agrawal, Nidhi; Vardhan, Harsh; Khokhar, Singh; Rai, Naresh; Saxena, Rajeev; Riyaz, Shahida

    2015-01-01

    Steroid cell tumors (SCTs) of the ovary are a rare subgroup of sex cord tumors that account for less than 0.1% of all ovarian tumors. These tumors can produce steroids, especially testosterone, which produces symptoms such as hirsutism, amenorrhea/oligomenorrhea, and male patterned voice. For evaluation of the androgen excess, testosterone and dehydroepiandrosterone sulfate (DHEA-S) are the first laboratory tests to be measured. Abdominal ultrasound and magnetic resonance imaging (MRI) are useful radiologic imaging techniques. Although SCTs are generally benign, the risk of malignant transformation is always present. Surgical excision of tumor is the most important and hallmark treatment. The present case signifies the early preoperative diagnosis of a virilizing SCT, based on cytological features and its careful correlation with clinicopathological and radiological findings. PMID:26811582

  18. Can Biomarker Assessment on Circulating Tumor Cells Help Direct Therapy in Metastatic Breast Cancer?

    PubMed Central

    Turner, Natalie; Pestrin, Marta; Galardi, Francesca; De Luca, Francesca; Malorni, Luca; Di Leo, Angelo

    2014-01-01

    Circulating tumor cell (CTC) count has prognostic significance in metastatic breast cancer, but the predictive utility of CTCs is uncertain. Molecular studies on CTCs have often been limited by a low number of CTCs isolated from a high background of leukocytes. Improved enrichment techniques are now allowing molecular characterisation of single CTCs, whereby molecular markers on single CTCs may provide a real-time assessment of tumor biomarker status from a blood test or “liquid biopsy”, potentially negating the need for a more invasive tissue biopsy. The predictive ability of CTC biomarker analysis has predominantly been assessed in relation to HER2, with variable and inconclusive results. Limited data exist for other biomarkers, such as the estrogen receptor. In addition to the need to define and validate the most accurate and reproducible method for CTC molecular analysis, the clinical relevance of biomarkers, including gain of HER2 on CTC after HER2 negative primary breast cancer, remains uncertain. This review summarises the currently available data relating to biomarker evaluation on CTCs and its role in directing management in metastatic breast cancer, discusses limitations, and outlines measures that may enable future development of this approach. PMID:24670368

  19. Ovarian malignant mixed germ cell tumor with clear cell carcinoma in a postmenopausal woman

    PubMed Central

    Yu, Xiu-Jie; Zhang, Lin; Liu, Zai-Ping; Shi, Yi-Quan; Liu, Yi-Xin

    2014-01-01

    Malignant germ cell tumors of the ovary are very rare and account for about 2-5% of all ovarian tumors of germ origin. Most patients are adolescent and young women, approximately two-thirds of them are under 20 years of age, occasionally in postmenopausal women. But clear cell carcinoma usually occurs in older patients (median age: 57-year old), and closely related with endometriosis. Here we report a case of a 55-year old woman with right ovarian mass that discovered by B ultrasonic. Her serum levels of human chorionic gonadotropin (hCG) and α-fetoprotein (AFP) were elevated. Pathological examination revealed the tumor to be a mixed germ cell tumor (yolk sac tumor, embryonal carcinoma and mature teratoma) with clear cell carcinoma in a background of endometriosis. Immunohistochemical staining showed SALL4 and PLAP were positive in germ cell tumor area, hCG, CD30 and OCT4 were positive in epithelial-like cells and giant synctiotrophoblastic cells, AFP, AAT, CD117 and Glyp3 were positive in yolk sac component, EMA and CK7 were positive in clear cell carcinoma, CD10 was positive in endometrial cells of endometriotic area. She was treated with surgery followed by seven courses of chemotherapy. She is well and serum levels of hCG and AFP have been decreased to normal levels. PMID:25674278

  20. Ovarian malignant mixed germ cell tumor with clear cell carcinoma in a postmenopausal woman.

    PubMed

    Yu, Xiu-Jie; Zhang, Lin; Liu, Zai-Ping; Shi, Yi-Quan; Liu, Yi-Xin

    2014-01-01

    Malignant germ cell tumors of the ovary are very rare and account for about 2-5% of all ovarian tumors of germ origin. Most patients are adolescent and young women, approximately two-thirds of them are under 20 years of age, occasionally in postmenopausal women. But clear cell carcinoma usually occurs in older patients (median age: 57-year old), and closely related with endometriosis. Here we report a case of a 55-year old woman with right ovarian mass that discovered by B ultrasonic. Her serum levels of human chorionic gonadotropin (hCG) and α-fetoprotein (AFP) were elevated. Pathological examination revealed the tumor to be a mixed germ cell tumor (yolk sac tumor, embryonal carcinoma and mature teratoma) with clear cell carcinoma in a background of endometriosis. Immunohistochemical staining showed SALL4 and PLAP were positive in germ cell tumor area, hCG, CD30 and OCT4 were positive in epithelial-like cells and giant synctiotrophoblastic cells, AFP, AAT, CD117 and Glyp3 were positive in yolk sac component, EMA and CK7 were positive in clear cell carcinoma, CD10 was positive in endometrial cells of endometriotic area. She was treated with surgery followed by seven courses of chemotherapy. She is well and serum levels of hCG and AFP have been decreased to normal levels. PMID:25674278

  1. Personalized ovarian cancer disease surveillance and detection of candidate therapeutic drug target in circulating tumor DNA.

    PubMed

    Martignetti, John A; Camacho-Vanegas, Olga; Priedigkeit, Nolan; Camacho, Catalina; Pereira, Elena; Lin, Li; Garnar-Wortzel, Leopold; Miller, Dagny; Losic, Bojan; Shah, Hardik; Liao, Jun; Ma, Jian; Lahiri, Pratik; Chee, Mark; Schadt, Eric; Dottino, Peter

    2014-01-01

    Retrospective studies have demonstrated that nearly 50% of patients with ovarian cancer with normal cancer antigen 125 (CA125) levels have persistent disease; however, prospectively distinguishing between patients is currently impossible. Here, we demonstrate that for one patient, with the first reported fibroblast growth factor receptor 2 (FGFR2) fusion transcript in ovarian cancer, circulating tumor DNA (ctDNA) is a more sensitive and specific biomarker than CA125, and it can also inform on a candidate therapeutic. For a 4-year period, during which the patient underwent primary debulking surgery and chemotherapy, tumor recurrences, and multiple chemotherapeutic regimens, blood samples were longitudinally collected and stored. Whereas postsurgical CA125 levels were elevated only three times for 28 measurements, the FGFR2 fusion ctDNA biomarker was readily detectable by quantitative real-time reverse transcription-polymerase chain reaction (PCR) in all of these same blood samples and in the tumor recurrences. Given the persistence of the FGFR2 fusion, we treated tumor cells derived from this patient and others with the FGFR2 inhibitor BGJ398. Only tumor cells derived from this patient were sensitive to FGFR2 inhibitor treatment. Using the same methodologic approach, we demonstrate in a second patient with a different fusion that PCR and agarose gel electrophoresis can also be used to identify tumor-specific DNA in the circulation. Taken together, we demonstrate that a relatively inexpensive, PCR-based ctDNA surveillance assay can outperform CA125 in identifying occult disease. PMID:24563622

  2. Inflammatory markers and risk of epithelial ovarian cancer by tumor subtypes: the EPIC cohort

    PubMed Central

    Ose, Jennifer; Schock, Helena; Tjonneland, Anne; Hansen, Louise; Overvad, Kim; Dossus, Laure; Clavel-Chapelon, Francoise; Baglietto, Laura; Boeing, Heiner; Trichopolou, Antonia; Benetou, Vassiliki; Lagiou, Pagona; Masala, Giovanna; Tagliabue, Giovanna; Tumino, Rosario; Sacerdote, Carlotta; Mattiello, Amalia; de Mesquita, H.Bas Bueno; Peeters, Petra H M; Onland-Moret, N Charlotte; Weiderpass, Elisabete; Gram, Inger T; Sánchez, Soledad; Obon-Santacana, Mireia; Sànchez-Pérez, Maria-José; Larrañaga, Nerea; Castaño, José María Huerta; Ardanaz, Eva; Brändstedt, Jenny; Lundin, Eva; Idahl, Annika; Travis, Ruth C; Khaw, Kay-Tee; Rinaldi, Sabina; Romieu, Isabelle; Merrit, Melissa A; Gunter, Marc J; Riboli, Elio; Kaaks, Rudolf; Fortner, Renée T

    2015-01-01

    Background Evidence suggests an etiologic role for inflammation in ovarian carcinogenesis and heterogeneity between tumor subtypes and anthropometric indices. Prospective studies on circulating inflammatory markers and epithelial invasive ovarian cancer (EOC) have predominantly investigated overall risk; data characterizing risk by tumor characteristics (histology, grade, stage, dualistic model of ovarian carcinogenesis) and anthropometric indices are sparse. Methods We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to evaluate C-reactive protein (CRP), interleukin-6 (IL-6), and EOC risk by tumor characteristics. A total of 754 eligible EOC cases were identified; two controls (n=1,497) were matched per case. We used multivariable conditional logistic regression to assess associations. Results CRP and IL-6 were not associated with overall EOC risk. However, consistent with prior research, CRP >10 vs. CRP ≤1 mg/L was associated with higher overall EOC risk (OR=1.67 [1.03 - 2.70]). We did not observe significant associations or heterogeneity in analyses by tumor characteristics. In analyses stratified by waist circumference, inflammatory markers were associated with higher risk among women with higher waist circumference; no association was observed for women with normal waist circumference: (e.g., IL-6: waist ≤80: ORlog2=0.97 [0.81 - 1.16]; waist >88: ORlog2=1.78 [1.28 - 2.48], pheterogeneity ≤0.01). Conclusions Our data suggest that high CRP is associated with increased risk of overall EOC, and that IL-6 and CRP may be associated with EOC risk among women with higher adiposity. Impact Our data add to global evidence that ovarian carcinogenesis may be promoted by an inflammatory milieu. PMID:25855626

  3. [Malignant ovarian tumors in childhood and adolescence in Novi Sad (1946-1989)].

    PubMed

    Berić, B; Gebauer, E; Dordević, M; Konstantinidis, N; Stojić, S

    1991-01-01

    In the period from 1946-1989, at the Department of Gynecology and Obstetrics University of Novi Sad, 79 ovarian tumors in children and adolescents were registered. There were 10 (12.6%) malignant tumours. The most common were dysgerminoma and carcinoma (total 6-7.6%). The treatment depended on the extent of the disease at the time of diagnosis (surgery, irradiation, chemotherapy or combination). PMID:1749284

  4. Multi-course PDT of malignant tumors: the influence on primary tumor, metastatic spreading and homeostasis of cancer patients

    NASA Astrophysics Data System (ADS)

    Sokolov, Victor V.; Chissov, Valery I.; Yakubovskaya, Raisa I.; Filonenko, E. V.; Sukhin, Garry M.; Nemtsova, E. R.; Belous, T. A.; Zharkova, Natalia N.

    1996-12-01

    The first clinical trials of photodynamic therapy (PDT) of cancer with two photosensitizers, PHOTOHEME and PHOTOSENS, were started in P.A. Hertzen Research Oncological Institute (Moscow, Russia) in 1992 and 1994. Up to now, 208 patients with primary, recurrent and metastatic malignant tumors (469) of skin (34 patients/185 tumors), breast cancer (24/101), head and neck (30/31), trachea and bronchus (31/42), esophagus (35/35), stomach (31/32), rectum (4/4), vagina and uterine cervix (7/8) and bladder (12/31) have been treated by PDT. One-hundred-thirty patients were injected with PHOTOHEME, 64 patients were injected with PHOTOSENS, 14 patients were injected with PHOTOHEME and PHOTOSENS. Totally, 302 courses of treatment were performed: 155 patients had one course and 53 patients were subjected to two to nine PDT sources with intervals from 1 to 18 months. A therapeutic effect of a one-course and multi- course PDT of malignant tumors (respiratory, digestive and urogenital systems) was evaluated clinically, histologically, roentgenologically, sonographically and endoscopically. The biochemical, hematological and immunological investigations were performed for all the patients in dynamics. Results of our study showed that a multi-course PDT method seems to be perspective in treatment of malignant tumors of basic localizations.

  5. An antibody to amphiregulin, an abundant growth factor in patients' fluids, inhibits ovarian tumors.

    PubMed

    Carvalho, S; Lindzen, M; Lauriola, M; Shirazi, N; Sinha, S; Abdul-Hai, A; Levanon, K; Korach, J; Barshack, I; Cohen, Y; Onn, A; Mills, G; Yarden, Y

    2016-01-28

    Growth factors of the epidermal growth factor (EGF)/neuregulin family are involved in tumor progression and, accordingly, antibodies that intercept a cognate receptor, epidermal growth factor receptor (EGFR)/ERBB1, or a co-receptor, HER2, have been approved for cancer therapy. Although they might improve safety and delay onset of chemoresistance, no anti-ligand antibodies have been clinically approved. To identify suitable ligands, we surveyed fluids from ovarian and lung cancer patients and found that amphiregulin (AREG) is the most abundant and generalized ligand secreted by advanced tumors. AREG is a low affinity EGFR ligand, which is upregulated following treatment with chemotherapeutic drugs. Because AREG depletion retarded growth of xenografted ovarian tumors in mice, we generated a neutralizing monoclonal anti-AREG antibody. The antibody inhibited growth of ovarian cancer xenografts and strongly enhanced chemotherapy efficacy. Taken together, these results raise the possibility that AREG and other low- or high-affinity binders of EGFR might serve as potential targets for cancer therapy. PMID:25915843

  6. Role of diffusion-weighted magnetic resonance imaging in differentiating malignancies from benign ovarian tumors

    PubMed Central

    Fan, Xinhua; Zhang, Hongbin; Meng, Shuang; Zhang, Jing; Zhang, Chuge

    2015-01-01

    Objective: We conducted a case-control study to evaluate the diagnostic values of computed tomography (CT) and diffusion-weighted magnetic resonance imaging (DW-MRI) in differentiating malignancies from benign ovarian tumors and a meta-analysis to further confirm our results on DW-MRI. Methods: Totally 64 patients pathologically confirmed as ovarian cancer were included in this study. CT scan and DWI-MRI were performed and analyzed to get compared with pathological results, thereby assessing their accuracy, sensitivity and specificity. Meta-analysis was conducted by database searching and strict eligibility criteria, using STATA 12.0 (Stata Corp, College Station, TX, USA) software. Results: The accuracy, sensitivity, specificity, positive predictive value and negative predictive value for diagnosis of ovarian cancer in CT were 81.82%, 84.48%, 76.67%, 87.50% and 71.88%, respectively; those in DW-MRI were 89.77%, 93.10%, 83.33%, 91.53% and 86.21%, respectively. The Kappa coefficient of DW-MRI (K = 0.771) compared with pathological results was higher than CT (K = 0.602). The average apparent diffusion coefficient values of DW-MRI in diagnosis of benign and malignant ovarian tumors suggested statistically significant difference (1.325 ± 0.269×10-3 mm2/s vs. 0.878 ± 0.246×10-3 mm2/s, P < 0.001). Meta-analysis results showed that the combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of DW-MRI in discriminating benign versus malignant ovarian tumors were 0.93, 0.88, 7.70, 0.08 and 101.24, respectively. The area under the summary receiver operating characteristic curve was 0.95. Conclusions: Both CT and DW-MRI were of great diagnostic value in differentiating malignancies from benign ovarian tumors, while DW-MRI was superior to CT with higher accuracy, sensitivity and specificity. PMID:26884905

  7. Palliative Care in Improving Quality of Life and Symptoms in Patients With Stage III-IV Pancreatic or Ovarian Cancer

    ClinicalTrials.gov

    2014-12-18

    Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Pancreatic Cancer

  8. c-Met inhibitors attenuate tumor growth of small cell hypercalcemic ovarian carcinoma (SCCOHT) populations.

    PubMed

    Otte, Anna; Rauprich, Finn; von der Ohe, Juliane; Yang, Yuanyuan; Kommoss, Friedrich; Feuerhake, Friedrich; Hillemanns, Peter; Hass, Ralf

    2015-10-13

    A cellular model (SCCOHT-1) of the aggressive small cell hypercalcemic ovarian carcinoma demonstrated constitutive chemokine and growth factor production including HGF. A simultaneous presence of c-Met in 41% SCCOHT-1 cells suggested an autocrine growth mechanism. Expression of c-Met was also observed at low levels in the corresponding BIN-67 cell line (6.5%) and at high levels in ovarian adenocarcinoma cells (NIH:OVCAR-3 (84.4%) and SK-OV-3 (99.3%)). Immunohistochemistry of c-Met expression in SCCOHT tumors revealed a heterogeneous distribution between undetectable levels and 80%. Further characterization of SCCOHT-1 and BIN-67 cells by cell surface markers including CD90 and EpCAM demonstrated similar patterns with differences to the ovarian adenocarcinoma cells. HGF stimulation of SCCOHT-1 cells was associated with c-Met phosphorylation at Tyr1349 and downstream Thr202/Tyr204 phosphorylation of p44/42 MAP kinase. This HGF-induced signaling cascade was abolished by the c-Met inhibitor foretinib. Cell cycle analysis after foretinib treatment demonstrated enhanced G2 accumulation and increasing apoptosis within 72 h. Moreover, the IC50 of foretinib revealed 12.4 nM in SCCOHT-1 cells compared to 411 nM and 481 nM in NIH:OVCAR-3 and SK-OV-3 cells, respectively, suggesting potential therapeutic effects. Indeed, SCCOHT-1 and BIN-67 tumor xenografts in NODscid mice exhibited an approximately 10-fold and 5-fold reduced tumor size following systemic application of foretinib, respectively. Furthermore, foretinib-treated tumors revealed a significantly reduced vascularization and little if any c-Met-mediated signal transduction. Similar findings of reduced proliferative capacity and declined tumor size were observed after siRNA-mediated c-Met knock-down in SCCOHT-1 cells demonstrating that in vivo inhibition of these pathways contributed to an attenuation of SCCOHT tumor growth. PMID:26436697

  9. c-Met inhibitors attenuate tumor growth of small cell hypercalcemic ovarian carcinoma (SCCOHT) populations

    PubMed Central

    Otte, Anna; Rauprich, Finn; von der Ohe, Juliane; Yang, Yuanyuan; Kommoss, Friedrich; Feuerhake, Friedrich; Hillemanns, Peter; Hass, Ralf

    2015-01-01

    A cellular model (SCCOHT-1) of the aggressive small cell hypercalcemic ovarian carcinoma demonstrated constitutive chemokine and growth factor production including HGF. A simultaneous presence of c-Met in 41% SCCOHT-1 cells suggested an autocrine growth mechanism. Expression of c-Met was also observed at low levels in the corresponding BIN-67 cell line (6.5%) and at high levels in ovarian adenocarcinoma cells (NIH:OVCAR-3 (84.4%) and SK-OV-3 (99.3%)). Immunohistochemistry of c-Met expression in SCCOHT tumors revealed a heterogeneous distribution between undetectable levels and 80%. Further characterization of SCCOHT-1 and BIN-67 cells by cell surface markers including CD90 and EpCAM demonstrated similar patterns with differences to the ovarian adenocarcinoma cells. HGF stimulation of SCCOHT-1 cells was associated with c-Met phosphorylation at Tyr1349 and downstream Thr202/Tyr204 phosphorylation of p44/42 MAP kinase. This HGF-induced signaling cascade was abolished by the c-Met inhibitor foretinib. Cell cycle analysis after foretinib treatment demonstrated enhanced G2 accumulation and increasing apoptosis within 72 h. Moreover, the IC50 of foretinib revealed 12.4 nM in SCCOHT-1 cells compared to 411 nM and 481 nM in NIH:OVCAR-3 and SK-OV-3 cells, respectively, suggesting potential therapeutic effects. Indeed, SCCOHT-1 and BIN-67 tumor xenografts in NODscid mice exhibited an approximately 10-fold and 5-fold reduced tumor size following systemic application of foretinib, respectively. Furthermore, foretinib-treated tumors revealed a significantly reduced vascularization and little if any c-Met-mediated signal transduction. Similar findings of reduced proliferative capacity and declined tumor size were observed after siRNA-mediated c-Met knock-down in SCCOHT-1 cells demonstrating that in vivo inhibition of these pathways contributed to an attenuation of SCCOHT tumor growth. PMID:26436697

  10. Elesclomol Sodium and Paclitaxel in Treating Patients With Recurrent or Persistent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2014-12-23

    Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Ovarian Carcinoma

  11. TLR8 Agonist VTX-2337 and Pegylated Liposomal Doxorubicin Hydrochloride or Paclitaxel in Treating Patients With Recurrent or Persistent Ovarian Epithelial, Fallopian Tube, or Peritoneal Cavity Cancer

    ClinicalTrials.gov

    2014-12-23

    Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Ovarian Carcinoma

  12. Clinical Outcomes of Gamma Knife Radiosurgery for Metastatic Brain Tumors from Gynecologic Cancer : Prognostic Factors in Local Treatment Failure and Survival

    PubMed Central

    Shin, Hong Kyung; Kim, Jeong Hoon; Lee, Do Heui; Cho, Young Hyun; Roh, Sung Woo

    2016-01-01

    Objective Brain metastases in gynecologic cancer (ovarian, endometrial, and cervical cancer) patients are rare, and the efficacy of Gamma Knife Radiosurgery (GKRS) to treat these had not been evaluated. We assessed the efficacy of GKRS and prognostic factors for tumor control and survival in brain metastasis from gynecologic cancers. Methods This retrospective study was approved by the institutional review board. From May 1995 to October 2012, 26 women (mean age 51.3 years, range 27–70 years) with metastatic brain tumors from gynecologic cancer were treated with GKRS. We reviewed their outcomes, radiological responses, and clinical status. Results In total 24 patients (59 lesions) were available for follow-up imaging. The median follow-up time was 9 months. The mean treated tumor volume at the time of GKRS was 8185 mm3 (range 10–19500 mm3), and the median dose delivered to the tumor margin was 25 Gy (range, 10–30 Gy). A local tumor control rate was 89.8% (53 of 59 tumors). The median overall survival was 9.5 months after GKRS (range, 1–102 months). Age-associated multivariate analysis indicated that the Karnofsky performance status (KPS), the recursive partitioning analysis (RPA) classification, and the number of treated lesions were significant prognostic factors for overall survival (HR=0.162, p=0.008, HR=0.107, p=0.038, and HR=2.897, p=0.045, respectively). Conclusion GKRS is safe and effective for the management of brain metastasis from gynecologic cancers. The clinical status of the patient is important in determining the overall survival time. PMID:27446522

  13. Prolonged Survival of a Patient With Pelvic Recurrence of Ovarian Malignant Mixed Mullerian Tumor After Chemoradiotherapy

    PubMed Central

    Homaei Shandiz, Fatemeh; Kadkhodayan, Sima; Hsanzade Mofrad, Malihe; Yousefi Roodsari, Zohre; Sharifi Sistani, Noorieh; Nabizadeh Marvast, Majid; Sadeghei, Mahbobe

    2014-01-01

    Introduction: Malignant Mixed Mullerian Tumor (MMMT) is a very rare tumor, accounting for less than 1% of all ovarian cancers. Case Presentation: We present a 64-year-old woman with stage III MMMT of ovary that was treated with platinum-based chemotherapy after optimal cytoreductive surgery. After 25 months of being disease free, she had a pelvic recurrence and a good response to chemoradiotherapy. Conclusions: Optimal cytoreductive surgery and chemotherapy may be the best treatment in MMMT but more discussion and experiences are needed regarding the effectiveness of radiotherapy. PMID:25593719

  14. Good things come in small packages: Therapeutic anti-tumor immunity induced by microRNA nanoparticles.

    PubMed

    Cubillos-Ruiz, Juan R; Sempere, Lorenzo F; Conejo-Garcia, Jose R

    2012-09-01

    Current ovarian cancer treatments based on surgery/chemotherapy show limited efficacy. Targeting immunosuppression is a requirement for the effectiveness of novel promising anti-tumor immunotherapies. Our latest work in preclinical models shows that nanoparticle-mediated delivery of immunostimulatory microRNAs specifically to tumor-associated leukocytes is sufficient to re-program immunological control of metastatic ovarian cancers. PMID:23162774

  15. Selective events in the metastatic process defined by analysis of the sequential dissemination of subpopulations of a mouse mammary tumor.

    PubMed

    Aslakson, C J; Miller, F R

    1992-03-15

    To identify selective steps in metastasis, those that eliminate nonmetastatic tumor cells more efficiently than metastatic cells, we have evaluated the sequential dissemination of tumor cells from a mammary fatpad, using both metastatic (4T1 and 66cl4) and nonmetastatic (67NR, 168FARN, and 4TO7) subpopulations of a single mouse mammary tumor. Each of these variant subpopulations is resistant to one or more selective drugs so they could be quantitatively identified by colony formation in selective media. We found that the 2 metastatic cell lines metastasized by different routes and that the nonmetastatic tumor cell lines failed at different points in dissemination. Line 67NR did not leave the primary site; clonogenic tumor cells were not detected in the nodes, blood, or lungs during the experiment (7 weeks). Tumor line 168FARN disseminated from the primary tumor because clonogenic cells were cultured from the draining lymph nodes throughout the experiment. However, dissemination essentially stopped in the node as cells were rarely isolated from blood, lungs, or lives. Whether 168FARN cells failed to reach these tissues or were killed very rapidly after traversing the lymph node is unknown. Line 4TO7 cells disseminated via the blood and were consistently recovered from lungs by day 19 but failed to proliferate. This panel of 5 subpopulations thus identifies different points of selective failure in tumor cell dissemination and should be valuable in the assessment of antimetastatic therapies. PMID:1540948

  16. Ovarian cancer survival by tumor dominance, a surrogate for site of origin

    PubMed Central

    Ivanova, Anna; Loo, Anneli; Tworoger, Shelley; Crum, Christopher P.; Fan, Isabel; McLaughlin, John R.; Rosen, Barry; Risch, Harvey; Narod, Steven A.; Kotsopoulos, Joanne

    2015-01-01

    Objectives Recent studies suggest that a proportion of ovarian tumors may actually originate in the distal fallopian tube. The objective of this study was to examine the relationship between dominance (a surrogate for site of origin) and survival following a diagnosis of epithelial ovarian cancer. Methods We classified 1,386 tumors as dominant (putatively originating in the ovary and non-dominant (putatively originating in the fallopian tube), using parameters obtained from pathology reports. Dominant tumors were restricted to one ovary or one involved ovary that exceeded the other in dimension by at least two-fold, while non-dominant tumors were identified as having a greater likelihood of a tubal origin if the disease was equally distributed across the ovaries. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) associated with dominance. Results Non-dominant tumors were more likely to be serous, stage III/IV, and be associated with a BRCA1/2 mutation, increasing parity and use of estrogen hormone replacement therapy (P ≤ 0.01). In contrast, 46% and 26% of the dominant tumors were serous and endometrioid, respectively, with a more even distribution of stage (P < 0.0001). Women with a non-dominant tumor had an increased risk of death compared to women with a dominant tumor (multivariate HR = 1.28; 95%CI 1.02–1.60). Findings were similar in our analysis restricted to serous only subtypes (HR = 1.28; 95%CI 1.01–1.63). Conclusion These preliminary findings suggest significantly worse survival among women diagnosed with a tumor putatively arising from fallopian tube. PMID:25771796

  17. Tumor metastases and cell-mediated immunity in a model system in DBA/2 mice. VIII. Expression and shedding of Fc gamma receptors on metastatic tumor cell variants.

    PubMed

    Schirrmacher, V; Jacobs, W

    1979-01-01

    The expression of receptors for the Fc portion of IgG immunoglobin molecules was studied on tumor cell lines with high and low metastatic capacity. Two tumor cell lines from DBA/2 mice that had high metastatic activity, ESb and MDAY-D2, contained a high percentage of Fc receptor positive cells, as detected in a rosette assay with IgG antibody-coated erythrocytes (EA). In contrast, the low metastatic parental line Eb, from which ESb was derived, contained only a low percentage of EA-rosette-forming cells. ESb ascites tumor cells adapted to tissue culture in the presence of 2-mercaptoethanol (2ME) had a high expression of Fc receptors, whereas a cell line adapted to tissue culture in the absence of 2ME had a low expression of Fc receptors. "Soluble" Fc receptors were detectable by their ability to bind to EA and to cause blocking of rosette formation. They were found to be present in fluids from tumor-bearing animals, such as serum and cell-free ascites. Even animals with an ascites tumor of the low-metastatic line Eb contained "soluble" Fc receptors. The results are discussed with regard to their possible significance for tumor metastasis. PMID:522481

  18. Ovarian mixed germ cell tumor with yolk sac and teratomatous components in a dog.

    PubMed

    Robinson, Nicholas A; Manivel, J Carlos; Olson, Erik J

    2013-05-01

    Mixed germ cell tumors of the ovary have rarely been reported in veterinary species. A 3-year-old intact female Labrador Retriever dog was presented for lethargy, abdominal distention, and a midabdominal mass. An exploratory laparotomy revealed a large (23 cm in diameter) left ovarian tumor and multiple small (2-3 cm in diameter) pale tan masses on the peritoneum and abdominal surface of the diaphragm. Histological examination of the left ovary revealed a mixed germ cell tumor with a yolk sac component with rare Schiller-Duval bodies and a teratomatous component comprised primarily of neural differentiation. The abdominal metastases were solely comprised of the yolk sac component. The yolk sac component was diffusely immunopositive for cytokeratin with scattered cells reactive for α-fetoprotein and placental alkaline phosphatase. Within the teratomatous component, the neuropil was diffusely immunopositive for S100, neuron-specific enolase, and neurofilaments with a few glial fibrillary acidic protein immunopositive cells. Ovarian germ cell tumors may be pure and consist of only 1 germ cell element or may be mixed and include more than 1 germ cell element, such as teratoma and yolk sac tumor. PMID:23604259

  19. Stereotactic body radiotherapy (SBRT) with or without surgery for primary and metastatic liver tumors

    PubMed Central

    Kirichenko, Alexander; Gayou, Olivier; Parda, David; Kudithipudi, Vijay; Tom, Kusum; Khan, Akhtar; Abrams, Peter; Szramowski, Molly; Oliva, Jose; Monga, Dulabh; Raj, Moses; Thai, Ngoc

    2015-01-01

    Objectives We report single center experience on the outcome and toxicity of SBRT alone or in combination with surgery for inoperable primary and metastatic liver tumors between 2007 and 2014. Patients and methods Patients with 1–4 hepatic lesions and tumor diameter ≤9 cm received SBRT at 46.8Gy ± 3.7 in 4–6 fractions. The primary end point was local control with at least 6 months of radiographic followup, and secondary end points were toxicity and survival. Results Eighty-seven assessable patients (114 lesions) completed liver SBRT for hepatoma (39) or isolated metastases (48) with a median followup of 20.3 months (range 1.9–64.1). Fourteen patients underwent liver transplant with SBRT as a bridging treatment or for tumor downsizing. Eight patients completed hepatic resections in combination with planned SBRT for unresectable tumors. Two-year local control was 96% for hepatoma and 93.8% for metastases; it was 100% for lesions ≤4 cm. Two-year overall survival was 82.3% (hepatoma) and 64.3% (metastases). No incidence of grade >2 treatment toxicity was observed. Conclusion In this retrospective analysis we demonstrate that liver SBRT alone or in combination with surgery is safe and effective for the treatment of isolated inoperable hepatic malignancies and provides excellent local control rates. PMID:26776856

  20. Targeting Angiogenesis and Tumor Microenvironment in Metastatic Colorectal Cancer: Role of Aflibercept

    PubMed Central

    Febbraro, Antonio; Venditti, Michele; Campidoglio, Serena; Olivieri, Nunzio; Raieta, Katia; Imbriani, Giusy Carmen; Remo, Andrea

    2014-01-01

    In the last decades, we have progressively observed an improvement in therapeutic options for metastatic colorectal cancer (mCRC) treatment with a progressive prolongation of survival. mCRC prognosis still remains poor with low percentage of 5-year survival. Targeted agents have improved results obtained with standard chemotherapy. Angiogenesis plays a crucial role in colorectal cancer growth, proliferation, and metastasization and it has been investigated as a potential target for mCRC treatment. Accordingly, novel antiangiogenic targeted agents bevacizumab, regorafenib, and aflibercept have been approved for mCRC treatment as the result of several phase III randomized trials. The development of a tumor permissive microenvironment via the aberrant expression by tumor cells of paracrine factors alters the tumor-stroma interactions inducing an expansion of proangiogenic signals. Recently, the VELOUR study showed that addition of aflibercept to FOLFIRI regimen as a second-line therapy for mCRC improved significantly OS, PFS, and RR. This molecule represents a valid second-line therapeutic option and its peculiar ability to interfere with placental growth factor (PlGF)/vascular endothelial growth factor receptor 1 (VEGFR1) axis makes it effective in targeting angiogenesis, inflammatory cells and in overcoming resistances to anti-angiogenic first-line treatment. Here, we discuss about Aflibercept peculiar ability to interfere with tumor microenvironment and angiogenic pathway. PMID:25136356

  1. Differentiation of Reactive and Tumor Metastatic Lymph Nodes with Diffusion-weighted and SPIO Enhanced MRI

    PubMed Central

    Zhang, Fan; Zhu, Lei; Huang, Xinglu; Niu, Gang; Chen, Siouan

    2012-01-01

    Objectives Determination of lymphatic metastasis is of great importance for both treatment planning and patient prognosis. We aim to distinguish tumor metastatic lymph nodes (TLNs) and reactive lymph nodes (RLNs) with diffusion-weighted and superparamagnetic iron oxide (SPIO) enhanced magnetic resonance imaging (MRI). Materials and methods Ipsilateral popliteal lymph node metastasis or lymphadenitis model was established by hock injection of either luciferase-expressing 4T1 murine breast cancer cells or Complete Freund Adjuvant (CFA) in male Balb/C mice. At different time points after inoculation, bioluminescence imaging, T2-weighted, diffusion-weighted and SPIO enhanced MRI were performed. Imaging findings were confirmed by histopathological staining. Results Size enlargement was observed in both TLNs and RLNs. At day 28, TLNs showed strong bioluminescence signal and bigger size than RLNs (p < 0.01). At early stages up to day 21, both TLNs and RLNs appeared homogeneous on diffusion-weighted imaging (DWI). At day 28, TLNs showed heterogeneous apparent diffusion coefficient (ADC) map with significantly higher average ADC value of 0.41 ± 0.03 × 10−3 mm2/s than that of RLNs (0.34 ± 0.02 10−3 mm2/s, p < 0.05). On SPIO enhanced MRI, both TLNs and RLNs showed distinct T2 signal reduction at day 21 after inoculation. At day 28, TLNs demonstrated partial uptake of the iron oxide particles, which was confirmed by Prussian blue staining. Conclusions Both diffusion-weighted and SPIO enhanced MRI can distinguish tumor metastatic lymph nodes from reactive lymph nodes. However, neither method is able to detect tumor metastasis to the draining lymph nodes at early stages. PMID:22588595

  2. Effect of pedicle fixation combined with 125I seed implantation for metastatic thoracolumbar tumors

    PubMed Central

    Qian, Jiale; Bao, Zhaohua; Zou, Jun; Yang, Huilin

    2016-01-01

    Purpose The aim of this study was to investigate the clinical efficacy of pedicle fixation combined with 125I brachytherapy in treating metastatic thoracolumbar tumors. Patients and methods A retrospective analysis of the clinical data of seven metastatic thoracolumbar tumor patients who received pedicle fixation combined with radioactive 125I seed implantation brachytherapy in our department between January 2009 and December 2013 was performed. The visual analog scale (VAS) for pain and the Karnofsky performance status (KPS) score before the operation and 1, 6, and 12 months after the operation were observed and recorded. The changes in the scores at each time point were compared. Results All the patients underwent a successful operation, without any complications during their hospitalization. All the patients received postoperative follow-up, and the duration of follow-up was 15–50 months, with an average of 32.2 months. One pancreatic cancer patient died of liver failure and hypoproteinemia 28 months post surgery. The VAS scores of patients before the operation and 1, 6, and 12 months after the operation were 7.43±0.98, 2.71±0.49, 3.00±0.82, and 4.29±0.98, respectively; the KPS scores were 52.9±9.5, 84.3±5.3, 75.7±5.3, and 72.9±4.9, respectively. These results suggest that the VAS score at each time point was significantly decreased compared with that before the operation, while the KPS score was significantly increased compared with that before the operation. Both differences had statistical significance (P<0.05). Conclusion As a therapy for advanced malignant tumors with thoracolumbar metastasis, pedicle fixation combined with 125I brachytherapy can effectively relieve short-term pain and improve patient’s quality of life. PMID:27274307

  3. Polyethylenimine-coated SPION exhibits potential intrinsic anti-metastatic properties inhibiting migration and invasion of pancreatic tumor cells.

    PubMed

    Mulens-Arias, Vladimir; Rojas, José Manuel; Pérez-Yagüe, Sonia; Morales, María del Puerto; Barber, Domingo F

    2015-10-28

    Due to its aggressive behavior, pancreatic cancer is one of the principal causes of cancer-related deaths. The highly metastatic potential of pancreatic tumor cells demands the development of more effective anti-metastatic approaches for this disease. Although polyethylenimine-coated superparamagnetic iron oxide nanoparticles (PEI-coated SPIONs) have been studied for their utility as transfection agents, little is known of their effect on tumor cell biology. Here we demonstrated that PEI-coated SPIONs have potent inhibitory effects on pancreatic tumor cell migration/invasion, through inhibition of Src kinase and decreased expression of MT1-MMP and MMP2 metalloproteinases. When treated with PEI-coated SPIONs, the pancreatic tumor cell line Pan02 showed reduced invadosome density and thus, a decrease in their ability to invade through basement membrane. These nanoparticles temporarily downmodulated microRNA-21, thereby upregulating the cell migration inhibitors PTEN, PDCD4 and Sprouty-1. PEI-coated SPIONs thus show intrinsic, possibly anti-metastatic properties for modulating pancreatic tumor cell migration machinery, which indicates their potential as anti-metastatic agents for treatment of pancreatic cancer. PMID:26264831

  4. Giant cell tumor of the pancreas arising in the ovarian-like stroma of a mucinous cystadenocarcinoma.

    PubMed

    Bergman, S; Medeiros, L J; Radr, T; Mangham, D C; Lewandrowski, K B

    1995-08-01

    We describe a malignant mucinous cystic neoplasm of the pancreas with ovarian-like stroma within which an osteoclast-like giant cell rich tumor arose. This rare tumor had a unique immunohistochemical profile with the giant cells staining for vimentin, leukocyte common antigen, and the monocyte/macrophage marker CD68, whereas the mucinous epithelium stained for epithelial membrane antigen and cytokeratin. The immunohistochemical findings are consistent with two lines of differentiation, one epithelial and the other suggesting mesenchymal differentiation of the giant cell tumor with an immunophenotype similar to giant cell tumor of bone. The coexistence of these two rare tumors suggests that they are histogenetically related. The findings of a giant cell tumor arising in the ovarian stroma indicates that the stroma of mucinous tumors is not always an innocuous component of the tumor. PMID:7594774

  5. NDN is an imprinted tumor suppressor gene that is downregulated in ovarian cancers through genetic and epigenetic mechanisms

    PubMed Central

    Yu, Yinhua; Mao, Weiqun; Wang, Yan; Baggerly, Keith; Wang, Ying; Marquez, Rebecca T.; Bedi, Anuja; Liu, Jinsong; Fishman, David; Lu, Zhen; Bast, Robert C.

    2016-01-01

    NDN is a maternally imprinted gene consistently expressed in normal ovarian epithelium, is dramatically downregulated in the majority of ovarian cancers. Little or no NDN expression could be detected in 73% of 351 epithelial ovarian cancers. NDN was also downregulated in 10 ovarian cancer cell lines with total loss in 6 of 10. Re-expression of NDN decreased Bcl-2 levels and induced apoptosis, which significantly inhibited ovarian cancer cell growth in cell culture and in xenografts. In addition, re-expression of NDN inhibited cell migration by decreasing actin stress fiber and focal adhesion complex formation through deactivation of Src, FAK and RhoA. Loss of NDN expression in ovarian cancers could be attributed to LOH in 28% of 18 informative cases and to hypermethylation of CpG sites 1 and 2 of NDN promoter in 23% and 30% of 43 ovarian cancers, respectively. Promoter hypermethylation was also found in 5 of 10 ovarian cancer cell lines. Treatment with the demethylating agent 5-aza-2′-deoxycytidine restored NDN expression in 4 of 7 cell lines with enhanced promoter methylation levels. These observations support the conclusion that NDN is an imprinted tumor suppressor gene which affects cancer cell motility, invasion and growth and that its loss of function in ovarian cancer can be caused by both genetic and epigenetic mechanisms. PMID:26689988

  6. Imprint cytology of high-grade immature ovarian teratoma: a case report, literature review, and distinction from other ovarian small round cell tumors.

    PubMed

    Ramalingam, Preetha; Teague, Daniel; Reid-Nicholson, Michelle

    2008-08-01

    Immature ovarian teratoma (IOT) is a rare and aggressive malignant neoplasm characterized by immature neural tissue. The cytomorphologic features have only rarely been described. We herein describe an additional case and review the literature regarding this entity. To the best of our knowledge, this is the first reported case with imprint cytology. A 35-year-old woman presented with a pelvic mass which was resected and sent for frozen section evaluation. Imprint smears and frozen section of the mass were diagnostic of IOT. IOT has diagnostic cytologic features which show complete concordance with histology. Differential diagnoses include other small round cell neoplasms such as ovarian neuroblastoma, small cell carcinoma of hypercalcemic type, primitive neuroectodermal tumor, Wilm's tumor, desmoplastic small round cell tumor, and Non-Hodgkin lymphoma. Distinguishing IOT from these tumors can be challenging however if diligent morphologic study and/or ancillary studies are performed accurate diagnosis is possible. PMID:18618728

  7. Self-targeting of TNF-releasing cancer cells in preclinical models of primary and metastatic tumors

    PubMed Central

    Dondossola, Eleonora; Dobroff, Andrey S.; Marchiò, Serena; Cardó-Vila, Marina; Hosoya, Hitomi; Libutti, Steven K.; Corti, Angelo; Sidman, Richard L.; Arap, Wadih; Pasqualini, Renata

    2016-01-01

    Circulating cancer cells can putatively colonize distant organs to form metastases or to reinfiltrate primary tumors themselves through a process termed “tumor self-seeding.” Here we exploit this biological attribute to deliver tumor necrosis factor alpha (TNF), a potent antitumor cytokine, directly to primary and metastatic tumors in a mechanism that we have defined as “tumor self-targeting.” For this purpose, we genetically engineered mouse mammary adenocarcinoma (TSA), melanoma (B16-F10), and Lewis lung carcinoma cells to produce and release murine TNF. In a series of intervention trials, systemic administration of TNF-expressing tumor cells was associated with reduced growth of both primary tumors and metastatic colonies in immunocompetent mice. We show that these malignant cells home to tumors, locally release TNF, damage neovascular endothelium, and induce massive cancer cell apoptosis. We also demonstrate that such tumor-cell–mediated delivery avoids or minimizes common side effects often associated with TNF-based therapy, such as acute inflammation and weight loss. Our study provides proof of concept that genetically modified circulating tumor cells may serve as targeted vectors to deliver anticancer agents. In a clinical context, this unique paradigm represents a personalized approach to be translated into applications potentially using patient-derived circulating tumor cells as self-targeted vectors for drug delivery. PMID:26858439

  8. Circulating tumor DNA to monitor treatment response and detect acquired resistance in patients with metastatic melanoma.

    PubMed

    Gray, Elin S; Rizos, Helen; Reid, Anna L; Boyd, Suzanah C; Pereira, Michelle R; Lo, Johnny; Tembe, Varsha; Freeman, James; Lee, Jenny H J; Scolyer, Richard A; Siew, Kelvin; Lomma, Chris; Cooper, Adam; Khattak, Muhammad A; Meniawy, Tarek M; Long, Georgina V; Carlino, Matteo S; Millward, Michael; Ziman, Melanie

    2015-12-01

    Repeat tumor biopsies to study genomic changes during therapy are difficult, invasive and data are confounded by tumoral heterogeneity. The analysis of circulating tumor DNA (ctDNA) can provide a non-invasive approach to assess prognosis and the genetic evolution of tumors in response to therapy. Mutation-specific droplet digital PCR was used to measure plasma concentrations of oncogenic BRAF and NRAS variants in 48 patients with advanced metastatic melanoma prior to treatment with targeted therapies (vemurafenib, dabrafenib or dabrafenib/trametinib combination) or immunotherapies (ipilimumab, nivolumab or pembrolizumab). Baseline ctDNA levels were evaluated relative to treatment response and progression-free survival (PFS). Tumor-associated ctDNA was detected in the plasma of 35/48 (73%) patients prior to treatment and lower ctDNA levels at this time point were significantly associated with response to treatment and prolonged PFS, irrespective of therapy type. Levels of ctDNA decreased significantly in patients treated with MAPK inhibitors (p < 0.001) in accordance with response to therapy, but this was not apparent in patients receiving immunotherapies. We show that circulating NRAS mutations, known to confer resistance to BRAF inhibitors, were detected in 3 of 7 (43%) patients progressing on kinase inhibitor therapy. Significantly, ctDNA rebound and circulating mutant NRAS preceded radiological detection of progressive disease. Our data demonstrate that ctDNA is a useful biomarker of response to kinase inhibitor therapy and can be used to monitor tumor evolution and detect the early appearance of resistance effectors. PMID:26524482

  9. Circulating tumor DNA to monitor treatment response and detect acquired resistance in patients with metastatic melanoma

    PubMed Central

    Gray, Elin S.; Rizos, Helen; Reid, Anna L.; Boyd, Suzanah C.; Pereira, Michelle R.; Lo, Johnny; Tembe, Varsha; Freeman, James; Lee, Jenny H.J.; Scolyer, Richard A.; Siew, Kelvin; Lomma, Chris; Cooper, Adam; Khattak, Muhammad A.; Meniawy, Tarek M.; Long, Georgina V.; Carlino, Matteo S.; Millward, Michael; Ziman, Melanie

    2015-01-01

    Repeat tumor biopsies to study genomic changes during therapy are difficult, invasive and data are confounded by tumoral heterogeneity. The analysis of circulating tumor DNA (ctDNA) can provide a non-invasive approach to assess prognosis and the genetic evolution of tumors in response to therapy. Mutation-specific droplet digital PCR was used to measure plasma concentrations of oncogenic BRAF and NRAS variants in 48 patients with advanced metastatic melanoma prior to treatment with targeted therapies (vemurafenib, dabrafenib or dabrafenib/trametinib combination) or immunotherapies (ipilimumab, nivolumab or pembrolizumab). Baseline ctDNA levels were evaluated relative to treatment response and progression-free survival (PFS). Tumor-associated ctDNA was detected in the plasma of 35/48 (73%) patients prior to treatment and lower ctDNA levels at this time point were significantly associated with response to treatment and prolonged PFS, irrespective of therapy type. Levels of ctDNA decreased significantly in patients treated with MAPK inhibitors (p < 0.001) in accordance with response to therapy, but this was not apparent in patients receiving immunotherapies. We show that circulating NRAS mutations, known to confer resistance to BRAF inhibitors, were detected in 3 of 7 (43%) patients progressing on kinase inhibitor therapy. Significantly, ctDNA rebound and circulating mutant NRAS preceded radiological detection of progressive disease. Our data demonstrate that ctDNA is a useful biomarker of response to kinase inhibitor therapy and can be used to monitor tumor evolution and detect the early appearance of resistance effectors. PMID:26524482

  10. Cyclophosphamide or Denileukin Diftitox Followed By Expanding a Patient's Own T Cells in the Laboratory in Treating Patients With HER-2/Neu Overexpressing Metastatic Breast Cancer, Ovarian Cancer, or Non-Small Cell Lung Cancer Previously Treated With HER-2/Neu Vaccine

    ClinicalTrials.gov

    2014-11-07

    HER2-positive Breast Cancer; Recurrent Breast Cancer; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Stage IV Breast Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor

  11. The expression of CK-19 gene in circulating tumor cells of blood samples of metastatic breast cancer women

    PubMed Central

    Soltani, Setareh; Mokarian, Fariborz; Panjehpour, Mojtaba

    2015-01-01

    Breast cancer is the most common cancer in women worldwide. Breast cancer in one third of all patients will go on to metastasis, which is the main cause of mortality in cancer cases. Tumor cells detach from primary tumor and enter into the circulation as circulating tumor cells (CTCs) which can form metastatic lesions. In this study, the expression of CK-19 gene in blood samples of metastatic breast cancer women was investigated and compared to control group. Twenty one patients with metastatic breast cancer and 20 healthy female volunteers enrolled in this study. For every patient and healthy donor 10 ml peripheral blood was collected. Peripheral blood mononuclear cells were isolated by gradient density centrifugation using Ficoll Hypaque. CK-19 gene expression was evaluated using SYBR green-based real-time quantitative polymerase chain reaction assays. The relative expression level of CK-19 was calculated using the 2−ΔΔCt analysis method. The mean of CK-19 expression was increased in metastatic breast cancer when compared to those of normal women (1.50 fold). 38.1% of the metastatic breast cancer patients showed CK-19 mRNA-detectable CTCs in their blood samples. There was no statistically significant difference between the relative expression level of CK-19 and the patient's clinicopathological characteristics. According to our knowledge, no study for determining CTC biomarkers in Iranian breast cancer women patients has yet been established. Our results suggest that the CK-19 mRNA expression investigation may be useful for monitoring CTCs in the blood of metastatic breast cancer patients, predicting early metastatic relapse or monitoring of anti-metastasis treatments. PMID:26779268

  12. Mature Ovarian Teratoma with Carcinoid Tumor in a 28-Year-Old Patient

    PubMed Central

    Petousis, Stamatios; Kalogiannidis, Ioannis; Margioula-Siarkou, Chrysoula; Traianos, Alexandros; Miliaras, Dimosthenis; Kamparoudis, Apostolos; Mamopoulos, Apostolos; Rousso, David

    2013-01-01

    Introduction. Coexistence of carcinoid tumor inside a mature cystic teratoma is an extremely rare phenomenon, especially in young women. We present the case of a 28-year-old woman diagnosed with a right ovarian carcinoid and treated uneventfully with conservative surgical approach. Case Report. A 28-year-old woman, gravid 0, parity 0, presented to our department for her annual gynecological examination and Pap smear test. During her examination, a mobile cystic mass was detected in the right lower abdomen. Ultrasound indicated a right ovarian mass 10.5 × 6.3 cm, confirmed by CT scan. Further investigation revealed AFP levels (1539 ng/mL). The ovarian mass was excised by laparoscopy, leaving intact the remaining right ovary. Frozen sections showed a mature cystic teratoma. However, paraffin sections revealed the presence of a small carcinoid within the teratoma's gastric-type mucosa. The patient was set to a close followup. Nine months postoperatively, ultrasound pelvis imaging and CT scan of the abdomen as well as serum tumor markers have shown no evidence of recurrence disease. Conclusion. Despite the weak evidence, fertility spare surgical approach for women wanting to preserve their genital tract might be a reasonable option. PMID:23984130

  13. 17β-estradiol inhibits spreading of metastatic cells from granulosa cell tumors through a non-genomic mechanism involving GPER1

    PubMed Central

    François, Charlotte M.; Wargnier, Richard; Petit, Florence; Goulvent, Thibaut; Rimokh, Ruth; Treilleux, Isabelle; Ray-Coquard, Isabelle; Zazzu, Valeria; Cohen-Tannoudji, Joëlle; Guigon, Céline J.

    2015-01-01

    Granulosa cell tumor (GCT) is a rare and severe form of sex-cord stromal ovarian tumor that is characterized by its long natural history and tendency to recur years after surgical ablation. Because there is no efficient curative treatment beyond surgery, ~20% of patients die of the consequences of their tumor. However, very little is known of the molecular etiology of this pathology. About 70% of GCT patients present with elevated circulating estradiol (E2). Because this hormone is known to increase tumor growth and progression in a number of cancers, we investigated the possible role of E2 in GCTs. Cell-based studies with human GCT metastases and primary tumor-derived cells, ie KGN and COV434 cells, respectively, aimed at evaluating E2 effect on cell growth, migration and invasion. Importantly, we found that E2 did not affect GCT cell growth, but that it significantly decreased the migration and matrix invasion of metastatic GCT cells. Noteworthy, our molecular studies revealed that this effect was accompanied by the inhibition through non-genomic mechanisms of extracellular signal-regulated kinase 1/2 (ERK1/2), which is constitutively activated in GCTs. By using pharmacological and RNA silencing approaches, we found that E2 action was mediated by G protein-coupled estrogen receptor 1 (GPER1) signaling pathway. Analyses of GPER1 expression on tissue microarrays from human GCTs confirmed its expression in ~90% of GCTs. Overall, our study reveals that E2 would act via non-classical pathways to prevent metastasis spreading in GCTs and also reveals GPER1 as a possible target in this disease. PMID:25823895

  14. 17β-estradiol inhibits spreading of metastatic cells from granulosa cell tumors through a non-genomic mechanism involving GPER1.

    PubMed

    François, Charlotte M; Wargnier, Richard; Petit, Florence; Goulvent, Thibaut; Rimokh, Ruth; Treilleux, Isabelle; Ray-Coquard, Isabelle; Zazzu, Valeria; Cohen-Tannoudji, Joëlle; Guigon, Céline J

    2015-05-01

    Granulosa cell tumor (GCT) is a rare and severe form of sex-cord stromal ovarian tumor that is characterized by its long natural history and tendency to recur years after surgical ablation. Because there is no efficient curative treatment beyond surgery, ~20% of patients die of the consequences of their tumor. However, very little is known of the molecular etiology of this pathology. About 70% of GCT patients present with elevated circulating estradiol (E2). Because this hormone is known to increase tumor growth and progression in a number of cancers, we investigated the possible role of E2 in GCTs. Cell-based studies with human GCT metastases and primary tumor-derived cells, ie KGN and COV434 cells, respectively, aimed at evaluating E2 effect on cell growth, migration and invasion. Importantly, we found that E2 did not affect GCT cell growth, but that it significantly decreased the migration and matrix invasion of metastatic GCT cells. Noteworthy, our molecular studies revealed that this effect was accompanied by the inhibition through non-genomic mechanisms of extracellular signal-regulated kinase 1/2 (ERK1/2), which is constitutively activated in GCTs. By using pharmacological and RNA silencing approaches, we found that E2 action was mediated by G protein-coupled estrogen receptor 1 (GPER1) signaling pathway. Analyses of GPER1 expression on tissue microarrays from human GCTs confirmed its expression in ~90% of GCTs. Overall, our study reveals that E2 would act via non-classical pathways to prevent metastasis spreading in GCTs and also reveals GPER1 as a possible target in this disease. PMID:25823895

  15. Multimodal Approach to the Management of Metastatic Epidural Spinal Cord Compression (MESCC) Due to Solid Tumors

    SciTech Connect

    Tancioni, Flavio; Navarria, Pierina; Lorenzetti, Martin A.; Pedrazzoli, Paolo; Masci, Giovanna; Mancosu, Pietro; Alloisio, Marco; Morenghi, Emanuela; Santoro, Armando; Rodriguez y Baena, Riccardo; Scorsetti, Marta

    2010-12-01

    Purpose: To assess the impact of a multidisciplinary approach for treatment of patients with metastatic epidural spinal cord compression in terms of feasibility, local control, and survival. Methods and Materials: Eighty-nine consecutive patients treated between January 2004 and December 2007 were included. The most common primary cancers were lung, breast, and kidney cancers. Ninety-eight surgical procedures were performed. Radiotherapy was performed within the first month postoperatively. Clinical outcome was evaluated by modified visual analog scale for pain, Frankel scale for neurologic deficit, and magnetic resonance imaging or computed tomography scan. Nearly all patients (93%) had back pain before treatment, whereas major or minor preoperative neurologic deficit was present in 62 cases (63%). Results: Clinical remission of pain was obtained in the vast majority of patients (91%). Improvement of neurologic deficit was observed in 45 cases (72.5%). Local relapse occurred in 10%. Median survival was 11 months (range, 0-46 months). Overall survival at 1 year was 43.6%. Type of primary tumor significantly affected survival. Conclusions: In patients with metastatic epidural spinal cord compression, the combination of surgery plus radiotherapy is feasible and provides clinical benefit in most patients. The discussion of each single case within a multidisciplinary team has been of pivotal importance in implementing the most appropriate therapeutic approach.

  16. Heterogeneity of tumor chemosensitivity in ovarian epithelial cancer revealed using the adenosine triphosphate-tumor chemosensitivity assay

    PubMed Central

    ZHANG, JIN; LI, HONGXIA

    2015-01-01

    Ovarian cancer has a poor prognosis, primarily due to the heterogeneity in chemosensitivity among patients. In the present study, this heterogeneity was evaluated in ovarian epithelial cancer (OEC) using an in vitro adenosine triphosphate tumor chemosensitivity assay (ATP-TCA). Specimens were collected from 80 patients who underwent cytoreductive surgery. Viable ovarian cancer cells obtained from malignant tissues were tested for sensitivity to paclitaxel (PTX), carboplatin (CBP), topotecan (TPT), gemcitabine (GEM), docetaxel (TXT), etoposide, bleomycin and 4-hydroperoxycyclophosphamide using ATP-TCA. The sensitivity, specificity, positive predictive value and negative predictive value for the clinical chemotherapy sensitivity of OEC were 88.6, 77.8, 83 and 84.8%, respectively. PTX demonstrated the highest sensitivity of all agents tested (82.5% in all specimens, 85.7% in recurrent specimens), followed by CBP (58.8 and 60.7%, respectively). The sensitivities to PTX and docetaxel (P<0.001) were correlated, in addition to those of CBP, TPT and GEM (P<0.001). Early-stage (I/II) and high- to mildly-differentiated OEC specimens revealed a lower chemosensitivity than advanced-stage (III) or low-differentiated specimens, respectively. The present study indicated that ATP-TCA is an effective method for guiding the choice of chemotherapy drugs. Notable heterogeneity of chemosensitivity was observed in the OEC specimens. PMID:26137074

  17. Isolated subcutaneous implantation of a borderline ovarian tumor: A case report and review of the literature.

    PubMed

    Banys-Paluchowski, Malgorzata; Yeganeh, Borsu; Luettges, Jutta; Maibach, Achim; Langenberg, Ruediger; Krawczyk, Natalia; Paluchowski, Peter; Maul, Holger; Gebauer, Gerhard

    2016-04-10

    Laparoscopy-related tumor implantations of gynecological malignancies into the subcutaneous tissue are rarely diagnosed. We report an interesting case of a 46-year-old female who presented with an abdominal subcutaneous metastasis of a borderline ovarian tumor. The patient received a laparoscopic unilateral adnexectomy for a solid-cystic tumor of the right ovary. Histopathological workup showed a papillary borderline tumor of mucinous type. Nine days later she underwent a hysterectomy, left adnexectomy, appendectomy and omentectomy. Exploration of the peritoneum revealed no intraperitoneal implants. Further exploration showed a non-invasive implant of a borderline tumor in the subcutaneous tissue above the fascia that had no contact to the peritoneum. It is hypothesized that tumor cells may have been implanted during a previous laparoscopy, the most recent of which had been fourteen years prior to her current presentation. Various risk factors for port-site malignancies have been identified. Tumor manipulation and extraction of tumor tissue without a protective bag may contribute to development of trocar-site metastasis. PMID:27081651

  18. Isolated subcutaneous implantation of a borderline ovarian tumor: A case report and review of the literature

    PubMed Central

    Banys-Paluchowski, Malgorzata; Yeganeh, Borsu; Luettges, Jutta; Maibach, Achim; Langenberg, Ruediger; Krawczyk, Natalia; Paluchowski, Peter; Maul, Holger; Gebauer, Gerhard

    2016-01-01

    Laparoscopy-related tumor implantations of gynecological malignancies into the subcutaneous tissue are rarely diagnosed. We report an interesting case of a 46-year-old female who presented with an abdominal subcutaneous metastasis of a borderline ovarian tumor. The patient received a laparoscopic unilateral adnexectomy for a solid-cystic tumor of the right ovary. Histopathological workup showed a papillary borderline tumor of mucinous type. Nine days later she underwent a hysterectomy, left adnexectomy, appendectomy and omentectomy. Exploration of the peritoneum revealed no intraperitoneal implants. Further exploration showed a non-invasive implant of a borderline tumor in the subcutaneous tissue above the fascia that had no contact to the peritoneum. It is hypothesized that tumor cells may have been implanted during a previous laparoscopy, the most recent of which had been fourteen years prior to her current presentation. Various risk factors for port-site malignancies have been identified. Tumor manipulation and extraction of tumor tissue without a protective bag may contribute to development of trocar-site metastasis. PMID:27081651

  19. Large moderately-differentiated ovarian Sertoli-Leydig cell tumor in a 13-year-old female: A case report

    PubMed Central

    ZHANG, HUI; HAO, JING; LI, CHUN-YAN; LI, TAO; MU, YU-LAN

    2016-01-01

    Sertoli-Leydig cell tumor of the ovary, also known as androblastoma, is a rare neoplasm from the group of sex cord-stromal tumors of the ovary. The tumor accounts for <0.5% of all primary ovarian neoplasms. The clinical signs and symptoms of Sertoli-Leydig cell tumors can be associated with either hormonal production or the presence of a mass-occupying lesion. In the current study, a 13-year-old female was diagnosed with a stage Ic ovarian Sertoli-Leydig cell tumor following abdominal pain and distension. One month after a right oophorectomy, the follow-up magnetic resonance imaging scan was negative for residual or recurrent tumor. The overall 5-year survival rate for moderately-differentiated (grade 2) and poorly-differentiated (grade 3) Sertoli-Leydig cell tumors is 80%, and long-term follow-up is therefore highly advised in this patient. PMID:26893701

  20. Tumor metastatic promoter ABCE1 interacts with the cytoskeleton protein actin and increases cell motility.

    PubMed

    Han, Xu; Tian, Ye; Tian, Dali

    2016-06-01

    ABCE1, a member of the ATP-binding cassette (ABC) family, is a candidate tumor metastatic promoter in lung cancer. Overexpression of ABCE1 is correlated with aggressive growth and metastasis in lung cancer cells. However, the exact mechanism remains unclear. In the present study, GST pull-down assay provided evidence of the possible interaction between ABCE1 and β-actin using GST-ABCE1 as a bait protein. Co-immunoprecipitation manifested ABCE1 formed complexes with β-actin in vivo. ABCE1 overexpression significantly increased the migration of lung cancer cells which may be attributed to the promotion of F-actin rearrangements. Taken together, these data suggest that overexpression of ABCE1 produces an obvious effect on the motility of lung cancer cells through cytoskeleton rearrangement. PMID:27109616

  1. Imaging Mitochondrial Redox Potential and Its Possible Link to Tumor Metastatic Potential

    PubMed Central

    Li, Lin Z.

    2012-01-01

    Cellular redox states can regulate cell metabolism, growth, differentiation, motility, apoptosis, signaling pathways, and gene expressions etc. Growing body of literature suggest importance of redox status for cancer progression. While most studies on redox state were done on cells and tissue lysates, it is important to understand the role of redox state in tissue in vivo/ex vivo and image its heterogeneity. Redox scanning is a clinically-translatable method for imaging tissue mitochondrial redox potential with a submillimeter resolution. Redox scanning data in mouse models of human cancers demonstrate a correlation between mitochondrial redox state and tumor metastatic potential. I will discuss the significance of this correlation and possible directions for future research. PMID:22895837

  2. Von Hippel Lindau disease with metastatic pancreatic neuroendocrine tumor causing ectopic Cushing's syndrome.

    PubMed

    Hatipoglu, Esra; Kepicoglu, Hasan; Rusen, Elif; Kabasakal, Levent; Gundogdu, Sadi; Kadioglu, Pinar

    2013-01-01

    We present a 39-year-old woman who was previously diagnosed with Von Hippel Lindau Disease (VHLD). She had surgery and radiotherapy for cranial hemangioblastoma (HA) 11 years ago and had unilateral adrenalectomy for pheochromocytoma in another hospital 6 month prior to her admission to our center. Moon face, buffalo hump, central obesity, progressive weight gain and menstrual irregularities persisted after adrenalectomy. Her laboratory results were consistent with ectopic Cushing's syndrome (ECS). A pancreatic solid mass with a nodule on the left lung were revealed upon computed tomography. In addition, Gallium-68 Somatostatin Receptor PET confirmed the pancreatic involvement and demonstrated additional lesions on the left lung and in the aortocaval lymphatic system on the right side, suggesting metastatic pancreatic neuroendocrine tumor (PNET). Peptide receptor radionuclide therapy (PRRT) with [177Lutetium-DOTA0,Tyr3] octreotate was performed on the patient, with no side effects observed. She was discharged from the hospital 10 days after the first cycle. PMID:23524618

  3. Treatment results of stereotactic interstitial brachytherapy for primary and metastatic brain tumors

    SciTech Connect

    Lucas, G.L.; Luxton, G.; Cohen, D.; Petrovich, Z.; Langholz, B.; Apuzzo, M.L.; Sapozink, M.D. )

    1991-08-01

    A total of 41 stereotactic interstitial brain implants in 39 patients were performed for recurrence after teletherapy (recurrence implant), or as part of initial treatment in conjunction with teletherapy (primary implant). Implanted tumors consisted of malignant gliomas (33), other primary brain tumors (3), and single metastatic lesions (3). All patients were temporarily implanted with Ir-192 using a coaxial catheter afterloading system; two patients were implanted twice. Survival post-implant for glioblastoma multiforme (GBM), 13 patients, was 10 months whether implanted primarily or for recurrence. Mean time to recurrence, measured from initiation of teletherapy to implantation, was 10 months. Twenty patients with anaplastic astrocytoma (AA) had a median survival post-implant of 23 months for primary implants (7 patients) and 11 months for recurrence implants (13 patients). Mean time to recurrence, measured from initiation of teletherapy to implantation, was 19 months. Three patients (9%) of the evaluable group required reoperation for symptomatic mass effect, all with initial diagnosis of AA. Survival for this subgroup was 14, 22, and 32 months post-implantation. Using stereotactic techniques, interstitial brachytherapy of brain tumors was technically feasible with negligible acute morbidity and mortality, and appeared to offer limited prolongation of control for a subset of patients with recurrent malignant gliomas. The role of this modality in primary treatment for malignant gliomas needs to be further defined by prospectively randomized trials.

  4. Primary Endometrial Yolk Sac Tumor With Endodermal-Intestinal Differentiation Masquerading as Metastatic Colorectal Adenocarcinoma.

    PubMed

    Damato, Stephen; Haldar, Krishnayan; McCluggage, W Glenn

    2016-07-01

    Yolk sac tumors (YSTs) with a somatic glandular pattern can be difficult to recognize histologically because they reproduce developing intestinal, hepatic, or lung tissue and can express markers such as CDX2 and TTF1. We report an unusual case of a primary endometrial YST showing florid endodermal-intestinal differentiation in a 63-yr-old woman with a history of colorectal adenocarcinoma. Histologically, the tumor exhibited a glandular and papillary architecture and showed widespread immunoreactivity for CDX2 and focal staining for CK20 and CEA, mimicking metastatic colorectal carcinoma on biopsy. The presence of subnuclear cytoplasmic clearing and positive staining for germ cell markers, however, pointed toward a diagnosis of primary endometrial YST, and this was supported by the radiologic and the subsequent pathologic finding of a primary endometrial-based lesion. YSTs in this age group usually arise in association with somatic tumors and in this case a small focus of coexistent endometrioid adenocarcinoma was identified within the uterus. Despite surgery and adjuvant chemotherapy, the patient showed disease progression with liver and lung metastases 6 mo postoperatively. PMID:26598980

  5. Diffuse melanosis after chemotherapy-induced tumor lysis syndrome in a patient with metastatic melanoma.

    PubMed

    Busam, Klaus J; Wolchok, Jedd; Jungbluth, Achim A; Chapman, Paul

    2004-03-01

    Diffuse melanosis is a rare event associated with advanced metastatic malignant melanoma. A 35-year-old woman with stage IV melanoma is presented, who developed slate bluish-gray to brown discoloration of her skin after chemotherapy-induced tumor lysis syndrome. A number of studies were performed to re-evaluate possible mechanisms of melanosis. Skin tissue was examined on routine hematoxylin-and-eosin-stained sections, Fontana stains, immunohistochemical studies with antibodies for Melan-A, gp100, tyrosinase, FXIIIa, and CD68, and by electron microscopy. The main cell types found to contain melanin pigment were histiocytes and dendritic cells. In the dermis, they were distributed mainly around venules. In the subcutaneous fat, they were scattered throughout the fat lobule. Melanin pigment was not only seen within cells but also extracellularly. No melanoma cells were seen in the skin. No increase in melanin pigment or number of melanocytes was seen in the epidermis. A bone marrow biopsy contained melanophages but no melanoma cells. Ultrastructural examination of the patient's serum revealed the presence of melanosomes. Sequence analysis of the tumor's cDNA failed to identify any mutations in the tyrosinase gene, and no tyrosinase protein was detected in non-melanocytic cells, indicating that it was unlikely that a mutation had resulted in a secretory form of the protein. These findings document that diffuse melanosis may result from tumor lysis, with release of melanosomes into the bloodstream. PMID:14984582

  6. The NOMS Framework: Approach to the Treatment of Spinal Metastatic Tumors

    PubMed Central

    Laufer, Ilya; Rubin, David G.; Lis, Eric; Cox, Brett W.; Stubblefield, Michael D.; Yamada, Yoshiya

    2013-01-01

    Background. Spinal metastases frequently arise in patients with cancer. Modern oncology provides numerous treatment options that include effective systemic, radiation, and surgical options. We delineate and provide the evidence for the neurologic, oncologic, mechanical, and systemic (NOMS) decision framework, which is used at Memorial Sloan-Kettering Cancer Center to determine the optimal therapy for patients with spine metastases. Methods. We provide a literature review of the integral publications that serve as the basis for the NOMS framework and report the results of systematic implementation of the NOMS-guided treatment. Results. The NOMS decision framework consists of the neurologic, oncologic, mechanical, and systemic considerations and incorporates the use of conventional external beam radiation, spinal stereotactic radiosurgery, and minimally invasive and open surgical interventions. Review of radiation oncology and surgical literature that examine the outcomes of treatment of spinal metastatic tumors provides support for the NOMS decision framework. Application of the NOMS paradigm integrates multimodality therapy to optimize local tumor control, pain relief, and restoration or preservation of neurologic function and minimizes morbidity in this often systemically ill patient population. Conclusion. NOMS paradigm provides a decision framework that incorporates sentinel decision points in the treatment of spinal metastases. Consideration of the tumor sensitivity to radiation in conjunction with the extent of epidural extension allows determination of the optimal radiation treatment and the need for surgical decompression. Mechanical stability of the spine and the systemic disease considerations further help determine the need and the feasibility of surgical intervention. PMID:23709750

  7. Is There a Role for PET/CT Parameters to Characterize Benign, Malignant, and Metastatic Parotid Tumors?

    PubMed Central

    Kendi, Ayse Tuba Karagulle; Magliocca, Kelly R.; Corey, Amanda; Galt, James R.; Switchenko, Jeffrey; Wadsworth, J. Trad; El-Deiry, Mark W.; Schuster, David M.; Saba, Nabil F.; Hudgins, Patricia A.

    2016-01-01

    OBJECTIVE Assessment of benign and malignant lesions of the parotid gland, including metastatic lesions, is challenging with current imaging methods. Fluorine-18 FDG PET/CT is a noninvasive imaging modality that provides both anatomic and metabolic information. Semiquantitative data obtained from PET/CT, also known as PET/CT parameters, are maximum, mean, or peak standardized uptake values (SUVs); metabolic tumor volume; total lesion glycolysis; standardized added metabolic activity; and normalized standardized added metabolic activity. Our aim was to determine whether FDG PET/CT parameters can differentiate benign, malignant, and metastatic parotid tumors. MATERIALS AND METHODS Thirty-four patients with parotid neoplasms underwent PET/CT before parotidectomy; maximum SUV, mean SUV, peak SUV, total lesion glycolysis, metabolic tumor volume, standardized added metabolic activity, and normalized standardized added metabolic activity were calculated on a dedicated workstation. Univariate analyses were performed. A ROC analysis was used to determine the ability of PET/CT parameters to predict pathologically proven benign, malignant, and metastatic parotid gland neoplasms. RESULTS Fourteen patients had a benign or malignant primary parotid tumor. Twenty had metastases to the parotid gland. When the specificity was set to at least 85% for each parameter to identify cut points, the corresponding sensitivities ranged from 15% to 40%. Assessment of benign versus malignant lesions of parotid tumors, as well as metastasis from squamous cell carcinoma versus other metastatic causes, revealed that none of the PET/CT parameters has enough power to differentiate among these groups. CONCLUSION PET/CT parameters, including total lesion glycolysis, metabolic tumor volume, standardized added metabolic activity, and normalized standardized added metabolic activity, are not able to differentiate benign from malignant parotid tumors, primary parotid tumors from metastasis, or metastasis

  8. High levels of EGFR expression in tumor stroma are associated with aggressive clinical features in epithelial ovarian cancer

    PubMed Central

    Wang, Ke; Li, Dan; Sun, Lu

    2016-01-01

    Purpose The aim of this study was to investigate the clinical significance and biological function of epidermal growth factor receptor (EGFR) expressed in tumor stroma of epithelial ovarian cancer. Methods Immunohistological staining of EGFR was evaluated in 242 patients with epithelial ovarian cancer. The correlations of EGFR expression in tumor stroma with clinicopathological features and with the expression level of Ki-67 were analyzed by SPSS software. Kaplan–Meier analysis and the Cox proportional hazard model were used to analyze the effect of EGFR expression in tumor stroma on the prognosis of patients with epithelial ovarian cancer. Meanwhile, the activities of proliferation and migration of tumor cells were detected when EGFR overexpressed in stroma cells. Results EGFR expression in tumor stroma correlated significantly with clinical stage (χ2=7.002, P=0.008) and distant metastases (χ2=16.59, P<0.001). Furthermore, there was a significantly positive correlation between the level of EGFR expressed in tumor stroma and the level of Ki-67 expressed in tumor cells (χ2=6.120, P=0.013). Patients with high EGFR expression level in tumor stroma showed poor survival (P=0.002). Multivariate analysis showed that high expression of EGFR in tumor stroma was an independent predictor for epithelial ovarian cancer patients (hazard ratio =1.703; 95% confidence interval 1.125–2.578, P=0.012). Furthermore, stroma cells overexpressing EGFR could promote the proliferation and migration of adjacent tumor cells. Conclusion High expression of EGFR in tumor stroma correlates with aggressive clinical features in epithelial ovarian cancer, and is an independent prognostic factor. PMID:26855586

  9. [The first experience in interstitial brachytherapy for primary and metastatic tumors of the brain].

    PubMed

    Bentsion, D L; Gvozdev, P B; Sakovich, V P; Fialko, N V; Kolotvinov, V S; Baiankina, S N

    2006-01-01

    In 2001-2002, the authors performed a course of brachytherapy in 15 patients with inoperable primary, recurrent, and metastatic brain tumors. The histostructural distribution was as follows: low-grade astrocytoma (grade II according to the WHO classification) in 2 patients, anaplastic astrocytoma (AA) in 3, glioblastoma multiforme (GBM) in 5. Five patients had solid tumor deposits in the brain. Computer tomographic (CT) and magnetic resonance imaging (MRI) data were used to define a path for forthcoming biopsy and implantation at a "Stryker" navigation station, by taking into account the anatomy of the brain, vessels, and functionally significant areas. After having histological findings, plastic intrastats whose number had been determined by the volume of a target were implanted into a tumor by the predetermined path. Dosimetric planning was accomplished by using CT and MRI images on an "Abacus" system. The final stage involved irradiation on a "GammaMed plus" with a source of 192Ir. Irradiation was given, by hyperfractionating its dose (3-4 Gy twice daily at an interval of 4-5 hours) to the total focal dose (TFD) of 36-44 Gy. Patients with gliomas untreated with radiation also underwent external radiation in a TFD of 54-56 Gy and patients with brain metastases received total external irradiation of the brain in a TFD of 36-40 Gy. The tolerance of a course of irradiation was fair. In patients with AA and GBM, one-year survival was observed in 66 and 60%, respectively; in those having metastasis, it was in 20%. Six patients died from progressive disease. All patients with low-grade astrocytoma and one patient with anaplastic astrocytoma were alive at month 24 after treatment termination. The mean lifespan of patients with malignant gliomas and solid tumor metastasis was 11.5 and 5.8 months, respectively. Brachytherapy is a noninvasive and tolerable mode of radiotherapy that increases survival in some groups of patients with inoperable brain tumors. PMID:16739930

  10. Overexpression of Membrane Proteins in Primary and Metastatic Gastrointestinal Neuroendocrine Tumors

    PubMed Central

    Wang, Donghong; Dahdaleh, Fadi S.; Bellizzi, Andrew M.; O’Dorisio, M. Sue; O’Dorisio, Thomas M.; Howe, James R.

    2014-01-01

    Background Small bowel and pancreatic neuroendocrine tumors (SBNETs and PNETs) are rare tumors whose incidence is increasing. Drugs targeting the somatostatin receptor are beneficial in these tumors. To identify additional cell-surface targets, we recently found receptors and membrane proteins with gene expression significantly different from adjacent normal tissues in a small number of primary SBNETs and PNETs. We set out to validate these expression differences in a large group of primary neuroendocrine tumors and to determine whether they are present in corresponding liver and lymph node metastases. Methods Primary SBNETs and PNETs, normal tissue, nodal, and liver metastases were collected and mRNA expression of six target genes was determined by quantitative PCR. Expression was normalized to GAPDH and POLR2A internal controls, and differences as compared to normal tissue were assessed by Welch’s t test. Results Gene expression was determined in 45 primary PNETs with 20 nodal and 17 liver metastases, and 51 SBNETs with 50 nodal and 29 liver metastases. Compared to normal tissue, the oxytocin receptor (OXTR) showed significant overexpression in both primary and metastatic SBNETs and PNETs. Significant overexpression was observed for MUC13 and MEP1B in PNET primary tumors, and for GPR113 in primary SBNETs and their metastases. SCTR and ADORA1 were significantly underexpressed in PNETs and their metastases. OXTR protein expression was confirmed by immunohistochemistry. Conclusions OXTR is significantly overexpressed relative to normal tissue in primary SBNETs and PNETs, and this overexpression is present in their liver and lymph node metastases, making OXTR a promising target for imaging and therapeutic interventions. PMID:24114056

  11. Dose Escalation for Metastatic Spinal Cord Compression in Patients With Relatively Radioresistant Tumors

    SciTech Connect

    Rades, Dirk; Freundt, Katja; Meyners, Thekla; Bajrovic, Amira; Basic, Hiba; Karstens, Johann H.; Adamietz, Irenaeus A.; Wildfang, Ingeborg; Rudat, Volker; Schild, Steven E.; Dunst, Juergen

    2011-08-01

    Purpose: Radiotherapy alone is the most common treatment for metastatic spinal cord compression (MSCC) from relatively radioresistant tumors such as renal cell carcinoma, colorectal cancer, and malignant melanoma. However, the results of the 'standard' regimen 30 Gy/10 fractions need to be improved with respect to functional outcome. This study investigated whether a dose escalation beyond 30 Gy can improve treatment outcomes. Methods and Materials: A total of 91 patients receiving 30 Gy/10 fractions were retrospectively compared to 115 patients receiving higher doses (37.5 Gy/15 fractions, 40 Gy/20 fractions) for motor function and local control of MSCC. Ten further potential prognostic factors were evaluated: age, gender, tumor type, performance status, number of involved vertebrae, visceral or other bone metastases, interval from tumor diagnosis to radiotherapy, pretreatment ambulatory status, and time developing motor deficits before radiotherapy. Results: Motor function improved in 18% of patients after 30 Gy and in 22% after higher doses (p = 0.81). On multivariate analysis, functional outcome was associated with visceral metastases (p = 0.030), interval from tumor diagnosis to radiotherapy (p = 0.010), and time developing motor deficits (p < 0.001). The 1-year local control rates were 76% after 30 Gy and 80% after higher doses, respectively (p = 0.64). On multivariate analysis, local control was significantly associated with visceral metastases (p = 0.029) and number of involved vertebrae (p = 0.043). Conclusions: Given the limitations of a retrospective study, escalation of the radiation dose beyond 30 Gy/10 fractions did not significantly improve motor function and local control of MSCC in patients with relatively radioresistant tumors.

  12. Chemokine axes in breast cancer: factors of the tumor microenvironment reshape the CCR7-driven metastatic spread of luminal-A breast tumors.

    PubMed

    Weitzenfeld, Polina; Kossover, Olga; Körner, Cindy; Meshel, Tsipi; Wiemann, Stefan; Seliktar, Dror; Legler, Daniel F; Ben-Baruch, Adit

    2016-06-01

    Chemokine axes have been shown to mediate site-specific metastasis in breast cancer, but their relevance to different subtypes has been hardly addressed. Here, with the focus on the CCR7-CCL21 axis, patient datasets demonstrated that luminal-A tumors express relatively low CCR7 levels compared with more aggressive disease subtypes. Furthermore, lymph node metastasis was not associated with high CCR7 levels in luminal-A patients. The metastatic pattern of luminal-A breast tumors may be influenced by the way luminal-A tumor cells interpret signals provided by factors of the primary tumor microenvironment. Thus, CCR7-expressing human luminal-A cells were stimulated simultaneously by factors representing 3 tumor microenvironment arms typical of luminal-A tumors, hormonal, inflammatory, and growth stimulating: estrogen + TNF-α + epidermal growth factor. Such tumor microenvironment stimulation down-regulated the migration of CCR7-expressing tumor cells toward CCL21 and inhibited the formation of directional protrusions toward CCL21 in a novel 3-dimensional hydrogel system. CCL21-induced migration of CCR7-expressing tumor cells depended on PI3K and MAPK activation; however, when CCR7-expressing cancer cells were prestimulated by tumor microenvironment factors, CCL21 could not effectively activate these signaling pathways. In vivo, pre-exposure of the tumor cells to tumor microenvironment factors has put restraints on CCL21-mediated lymph node-homing cues and shifted the metastatic pattern of CCR7-expressing cells to the aggressive phenotype of dissemination to bones. Several of the aspects were also studied in the CXCR4-CXCL12 system, demonstrating similar patient and in vitro findings. Thus, we provide novel evidence to subtype-specific regulation of the CCR7-CCL21 axis, with more general implications to chemokine-dependent patterns of metastatic spread, revealing differential regulation in the luminal-A subtype. PMID:26936935

  13. Overexpression of GAB2 in ovarian cancer cells promotes tumor growth and angiogenesis by upregulating chemokine expression

    PubMed Central

    Duckworth, C; Zhang, L; Carroll, S L; Ethier, S P; Cheung, H W

    2016-01-01

    We previously found that the scaffold adapter GRB2-associated binding protein 2 (GAB2) is amplified and overexpressed in a subset of primary high-grade serous ovarian cancers and cell lines. Ovarian cancer cells overexpressing GAB2 are dependent on GAB2 for activation of the phosphatidylinositol 3-kinase (PI3K) pathway and are sensitive to PI3K inhibition. In this study, we show an important role of GAB2 overexpression in promoting tumor angiogenesis by upregulating expression of multiple chemokines. Specifically, we found that suppression of GAB2 by inducible small hairpin RNA in ovarian cancer cells inhibited tumor cell proliferation, angiogenesis and peritoneal tumor growth in immunodeficient mice. Overexpression of GAB2 upregulated the secretion of several chemokines from ovarian cancer cells, including CXCL1, CXCL2 and CXCL8. The secreted chemokines not only signal through endothelial CXCR2 receptor in a paracrine manner to promote endothelial tube formation, but also act as autocrine growth factors for GAB2-induced transformation of fallopian tube secretory epithelial cells and clonogenic growth of ovarian cancer cells overexpressing GAB2. Pharmacological inhibition of inhibitor of nuclear factor kappa-B kinase subunit β (IKKβ), but not PI3K, mechanistic target of rapamycin (mTOR) or mitogen-activated protein kinase (MEK), could effectively suppress GAB2-induced chemokine expression. Inhibition of IKKβ augmented the efficacy of PI3K/mTOR inhibition in suppressing clonogenic growth of ovarian cancer cells with GAB2 overexpression. Taken together, these findings suggest that overexpression of GAB2 in ovarian cancer cells promotes tumor growth and angiogenesis by upregulating expression of CXCL1, CXCL2 and CXCL8 that is IKKβ-dependent. Co-targeting IKKβ and PI3K pathways downstream of GAB2 might be a promising therapeutic strategy for ovarian cancer that overexpresses GAB2. PMID:26657155

  14. Overexpression of GAB2 in ovarian cancer cells promotes tumor growth and angiogenesis by upregulating chemokine expression.

    PubMed

    Duckworth, C; Zhang, L; Carroll, S L; Ethier, S P; Cheung, H W

    2016-08-01

    We previously found that the scaffold adapter GRB2-associated binding protein 2 (GAB2) is amplified and overexpressed in a subset of primary high-grade serous ovarian cancers and cell lines. Ovarian cancer cells overexpressing GAB2 are dependent on GAB2 for activation of the phosphatidylinositol 3-kinase (PI3K) pathway and are sensitive to PI3K inhibition. In this study, we show an important role of GAB2 overexpression in promoting tumor angiogenesis by upregulating expression of multiple chemokines. Specifically, we found that suppression of GAB2 by inducible small hairpin RNA in ovarian cancer cells inhibited tumor cell proliferation, angiogenesis and peritoneal tumor growth in immunodeficient mice. Overexpression of GAB2 upregulated the secretion of several chemokines from ovarian cancer cells, including CXCL1, CXCL2 and CXCL8. The secreted chemokines not only signal through endothelial CXCR2 receptor in a paracrine manner to promote endothelial tube formation, but also act as autocrine growth factors for GAB2-induced transformation of fallopian tube secretory epithelial cells and clonogenic growth of ovarian cancer cells overexpressing GAB2. Pharmacological inhibition of inhibitor of nuclear factor kappa-B kinase subunit β (IKKβ), but not PI3K, mechanistic target of rapamycin (mTOR) or mitogen-activated protein kinase (MEK), could effectively suppress GAB2-induced chemokine expression. Inhibition of IKKβ augmented the efficacy of PI3K/mTOR inhibition in suppressing clonogenic growth of ovarian cancer cells with GAB2 overexpression. Taken together, these findings suggest that overexpression of GAB2 in ovarian cancer cells promotes tumor growth and angiogenesis by upregulating expression of CXCL1, CXCL2 and CXCL8 that is IKKβ-dependent. Co-targeting IKKβ and PI3K pathways downstream of GAB2 might be a promising therapeutic strategy for ovarian cancer that overexpresses GAB2. PMID:26657155

  15. Clinical efficacy of computed tomography-guided iodine-125 seed implantation therapy in patients with advanced spinal metastatic tumors

    PubMed Central

    Zhang, Liyun; Lu, Jian; Wang, Zhongmin; Cheng, Yingsheng; Teng, Gaojun; Chen, Kemin

    2016-01-01

    Objective The purpose of this study was to examine the safety and clinical efficacy of computed tomography (CT)-guided radioactive iodine-125 (125I) seed implantation treatment in patients with spinal metastatic tumors. Methods We retrospectively analyzed 20 cases of spinal metastatic tumors, including nine men and eleven women aged 50–79 years (mean age: 61.1 years). We used treatment planning system (TPS) to construct three-dimensional images of the spinal metastatic tumors and to determine what number and dose rate distribution to use for the 125I seeds. The matched peripheral dose of the 125I seed implantation was 90–130 Gy. Twenty-four spinal metastatic tumors were treated by CT-guided radioactive 125I seed implantation. A median of 19 (range: 4–43) 125I seeds were implanted. Results Twenty cases were followed for a median of 15.3 months (range: 7–32 months). The rate of pain relief was 95%. The median control time for all of the patients was 12.5 months. The 3-, 6-, and 12-month cumulative local control rates were 100%, 95%, and 60%, respectively. The median survival time for all of the patients was 16 months. The cumulative 6- and 12-month survival rates were 100% and 78.81%, respectively. No major complications were observed. No 125I seeds were lost or migrated to other tissues or organs. Conclusion CT-guided radioactive 125I seed implantation is a safe, effective, and minimally invasive method for the treatment of patients with spinal metastatic tumors. It is a possible alternative therapy for the treatment of spinal metastases. PMID:26719712

  16. Virilizing ovarian stromal tumor in a young woman with Carney complex.

    PubMed

    Carney, J Aidan; Stratakis, Constantine A

    2011-10-01

    A woman with Carney complex presented at the age of 22 years with abdominal pain and hirsutism. As a baby, she had undergone excision of a right eyelid lesion, and at age 14 years she had undergone removal of a left lower eyelid nodule that subsequently recurred. Investigation revealed an elevated level of serum testosterone and a 2-cm left ovarian tumor. A left salpingo-oophorectomy was performed. Postoperatively, she experienced relief from abdominal pain, the serum level of testosterone normalized, and the hirsutism ameliorated. The tumor featured sheets of eosinophilic cells with lipochrome pigment, myeloid metaplasia, stromal metaplasia, and markedly abnormal blood vessels. Immunocytochemically, the tumor cells were positive for vimentin, synaptophysin, inhibin-A, and calrenin. Because of the clinical setting in which the neoplasm occurred, it is likely that is occurrence was related to Carney complex. PMID:21934476

  17. A Quick Responsive Fluorogenic pH Probe for Ovarian Tumor Imaging

    PubMed Central

    Tung, Ching-Hsuan; Qi, Jianjun; Hu, Lingchuan; Han, Myung Shin; Kim, Young

    2015-01-01

    A novel cell-permeable compound, CypH-1, that is non-fluorescent at neutral pH, but fluoresces under mildly acidic conditions with a near infrared maximum emission wavelength was designed for the detection of tumors in the clinical setting. The potential of CypH-1 in ovarian cancer imaging was demonstrated using a murine model. The intraperitoneally administered CypH-1 results in a robust fluorescence signal of discrete neoplastic lesions with millimeter range resolution within few hours. Moreover, fluorescence signal is strikingly enhanced at peripheral regions of tumors at the microscopic level suggesting a sharp physiological difference at the tumor/normal tissue interface. This robust acid-activated imaging agent is expected to have significant impact in broad surgical and diagnostic applications. PMID:26284146

  18. Metastatic Cancer

    MedlinePlus

    ... cancers, including cancers of the blood and the lymphatic system ( leukemia , multiple myeloma , and lymphoma ), can form metastatic tumors. Although rare, the metastasis of blood and lymphatic system cancers to the lung, heart, central nervous system , ...

  19. Fine needle aspiration cytology of cervical lymph node involvement by ovarian serous borderline tumor

    PubMed Central

    Chen, Longwen; Butler, Kristina A.; Bell, Debra A.

    2016-01-01

    Serous borderline tumor (SBT) involving a cervical lymph node is extremely rare. In addition, fine needle aspiration (FNA) cytology of the involved cervical lymph node shares tremendous morphologic similarity with other low-grade papillary carcinomas. Thus, it can be easily misdiagnosed as metastatic carcinoma. A 42-year-old female had a history of bilateral SBT and postbilateral salpingo-oophorectomy. She presented with left cervical lymphadenopathy 6 months later. FNA cytology showed a low-grade papillary neoplasm with psammoma bodies. Needle core biopsy along with immunostains was diagnostic of cervical lymph node involvement (LNI) of SBT. although extremely rare, cervical LNI can be found in patients with SBTs. FNA cytology, sometimes, is indistinguishable from metastatic papillary adenocarcinoma. Cell block or needle core biopsy is essential to make the correct diagnosis.

  20. A Cross-Sectional Comparison of Druggable Mutations in Primary Tumors, Metastatic Tissue, Circulating Tumor Cells, and Cell-Free Circulating DNA in Patients with Metastatic Breast Cancer: The MIRROR Study Protocol

    PubMed Central

    Picornell, Antoni C; Alvarez, Enrique L; Martin, Miguel

    2016-01-01

    Background Characterization of the driver mutations in an individual metastatic breast cancer (MBC) patient is critical to selecting effective targeted therapies. Currently, it is believed that the limited efficacy of many targeted drugs may be due to the expansion of drug resistant clones with different genotypes that were already present in the primary tumor. Identifying the genomic alterations of these clones, and introducing combined or sequential targeted drug regimens, could lead to a significant increase in the efficacy of currently available targeted therapies. Objective The primary objective of this study is to assess the concordance/discordance of mutations between the primary tumor and metastatic tissue in MBC patients. Secondary objectives include comparing the genomic profiles of circulating tumor cells (CTCs) and circulating free DNA (cfDNA) from peripheral blood with those of the primary tumor and metastatic tissue for each patient, evaluating these mutations in the signaling pathways that are relevant to the disease, and testing the feasibility of introducing liquid biopsy as a translational laboratory tool in clinical practice. Methods The multicenter, transversal, observational MIRROR study is currently ongoing in three participating hospitals. All consecutive patients with MBC confirmed by radiologic findings will be screened for eligibility, either at first relapse or if tumor regrowth occurs while on treatment for metastatic disease. Results Patient recruitment is currently ongoing. To date, 41 patients have a complete set of tissue samples available (plasma, CTCs, and formalin-fixed, paraffin-embedded primary tumor and metastatic tumor). However, none of these samples have undergone nucleic acids extraction or targeted deep sequencing. Conclusions The results of this study may have a significant influence on the practical management of patients with MBC, and may provide clues to clinicians that lead towards a better stratification of patients

  1. Dietary Selenium Supplementation Modulates Growth of Brain Metastatic Tumors and Changes the Expression of Adhesion Molecules in Brain Microvessels.

    PubMed

    Wrobel, Jagoda K; Wolff, Gretchen; Xiao, Rijin; Power, Ronan F; Toborek, Michal

    2016-08-01

    Various dietary agents can modulate tumor invasiveness. The current study explored whether selenoglycoproteins (SeGPs) extracted from selenium-enriched yeast affect tumor cell homing and growth in the brain. Mice were fed diets enriched with specific SeGPs (SeGP40 or SeGP65, 1 mg/kg Se each), glycoproteins (GP40 or GP65, 0.2-0.3 mg/kg Se each) or a control diet (0.2-0.3 mg/kg Se) for 12 weeks. Then, murine Lewis lung carcinoma cells were infused into the brain circulation. Analyses were performed at early (48 h) and late stages (3 weeks) post tumor cell infusion. Imaging of tumor progression in the brain revealed that mice fed SeGP65-enriched diet displayed diminished metastatic tumor growth, fewer extravasating tumor cells and smaller metastatic lesions. While administration of tumor cells resulted in a significant upregulation of adhesion molecules in the early stage of tumor progression, overexpression of VCAM-1 (vascular call adhesion molecule-1) and ALCAM (activated leukocyte cell adhesion molecule) messenger RNA (mRNA) was diminished in SeGP65 supplemented mice. Additionally, mice fed SeGP65 showed decreased expression of acetylated NF-κB p65, 48 h post tumor cell infusion. The results indicate that tumor progression in the brain can be modulated by specific SeGPs. Selenium-containing compounds were more effective than their glycoprotein controls, implicating selenium as a potential negative regulator of metastatic process. PMID:26706037

  2. An Ovarian Carcinoid Tumor With Peptide YY-Positive Insular Component: A Case Report and Review of the Literature.

    PubMed

    Erdenebaatar, Chimeddulam; Yamaguchi, Munekage; Saito, Fumitaka; Motooka, Chisato; Tashiro, Hironori; Katabuchi, Hidetaka

    2016-07-01

    Ovarian carcinoid tumors are uncommon and account for 1% of all carcinoid tumors. The insular type of ovarian carcinoid tumor is common in western countries; in contrast, the strumal and trabecular types seem to be common in Asian countries. Strumal and trabecular types are associated with peptide YY (PYY) production, which may cause constipation. Here, we report the case of a 70-yr-old Japanese woman with chronic constipation who was referred to Kumamoto University Hospital because of a right adnexal mass. Imaging tests suggested that the solid mass might be malignant; therefore, abdominal total hysterectomy, bilateral salpingo-oophorectomy, and omentectomy were performed. A subsequent histopathologic examination confirmed an insular carcinoid tumor with a trabecular component in the right ovary. Both components were positive for PYY but not for serotonin. The patient complained of diarrhea instead of constipation soon after the surgery. Because PYY-positive insular carcinoid tumor in the ovary has not been previously reported, we reviewed 19 reported cases of patients with PYY-positive ovarian carcinoid tumors. The origins, common histologic types and symptoms caused by specific peptides secreted in ovarian carcinoid tumors differ between western and Asian countries. PMID:26630222

  3. Deregulated miR-296/S100A4 axis promotes tumor invasion by inducing epithelial-mesenchymal transition in human ovarian cancer

    PubMed Central

    Yan, Wang; Chen, Jiaqi; Chen, Zhaoying; Chen, Huimin

    2016-01-01

    S100A4 represents an important member of the S100 family of small calcium-binding proteins. Increased expression of S100A4 has been observed in chronic inflammatory and autoimmune diseases, such as idiopathic inflammatory myopathies. The majority of studies of S100A4 are focused on cancer research; however, the oncogenic roles of S100A4 in epithelial ovarian cancer (EOC) remain largely unexplored. In this study, S100A4 expression is significantly up-regulated in ovarian cancer and associated with the clinical stage of EOC patients. Attenuation of S100A4 expression results in decreased cell mobility and metastatic capacity, whereas overexpression of S100A4 enhanced the invasive ability of EOC cells. Then by an integrated informatics analysis and luciferase reporter assay, we identify that miR-296 is a critical upstream regulator of S100A4. In addition, deregulated miR-296/S100A4 axis facilitates epithelial-mesenchymal transition (EMT) process as demonstrated by altered expression of EMT-related markers. In conclusion, our study reveals that deregulated miR-296/S100A4 promotes tumor progression in EOC, and provides evidence that miR-296/S100A4 axis-related signaling may represent a potential target for EOC therapy. PMID:27186401

  4. Surgery Followed by Radiotherapy Versus Radiotherapy Alone for Metastatic Spinal Cord Compression From Unfavorable Tumors

    SciTech Connect

    Rades, Dirk; Huttenlocher, Stefan; Bajrovic, Amira; Karstens, Johann H.; Adamietz, Irenaeus A.; Kazic, Nadja; Rudat, Volker; Schild, Steven E.

    2011-12-01

    Purpose: Despite a previously published randomized trial, controversy exists regarding the benefit of adding surgery to radiotherapy for metastatic spinal cord compression (MSCC). It is thought that patients with MSCC from relatively radioresistant tumors or tumors associated with poor functional outcome after radiotherapy alone may benefit from surgery. This study focuses on these tumors. Methods and Materials: Data from 67 patients receiving surgery plus radiotherapy (S+RT) were matched to 134 patients (1:2) receiving radiotherapy alone (RT). Groups were matched for 10 factors and compared for motor function, ambulatory status, local control, and survival. Additional separate matched-pair analyses were performed for patients receiving direct decompressive surgery plus stabilization of involved vertebrae (DDSS) and patients receiving laminectomy (LE). Results: Improvement of motor function occurred in 22% of patients after S+RT and 16% after RT (p = 0.25). Posttreatment ambulatory rates were 67% and 61%, respectively (p = 0.68). Of nonambulatory patients, 29% and 19% (p = 0.53) regained ambulatory status. One-year local control rates were 85% and 89% (p = 0.87). One-year survival rates were 38% and 24% (p = 0.20). The matched-pair analysis of patients receiving LE showed no significant differences between both therapies. In the matched-pair analysis of patients receiving DDSS, improvement of motor function occurred more often after DDSS+RT than RT (28% vs. 19%, p = 0.024). Posttreatment ambulatory rates were 86% and 67% (p = 0.30); 45% and 18% of patients regained ambulatory status (p = 0.29). Conclusions: Patients with MSCC from an unfavorable primary tumor appeared to benefit from DDSS but not LE when added to radiotherapy in terms of improved functional outcome.

  5. Ovarian Malignant Mixed Germ Cell Tumor: A Case of Unusual Presentation as Molar Pregnancy

    PubMed Central

    Aminimoghaddam, Soheila; Mohseni, Iman; Afzalzadeh, Azadeh; Esmaeeli, Shooka

    2016-01-01

    Background: This research was conducted to introduce a patient with rare ovarian mixed germ cell tumor, presented as molar pregnancy. Case Presentation: The patient was a 16 year old woman admitted with diagnosis of molar pregnancy. Abdominal enlargement was the only complaint. She had a large pelvic mass in physical examination. The first diagnosis was molar pregnancy due to previous ultrasonic reports and positive βeta HCG. Urine pregnancy test was positive. As suction curettage was performed for her, surprisingly, the size of uterus was normal and no molar tissue was found in pathologic examination. At intraoperative ultrasound exam, an extra-uterine heterogeneous mass was found. Extra-uterine mass was confirmed by CT and MRI done after suction curettage. Mixed germ cell tumor was confirmed by histological examination after laparatomy and removing tumoral mass. Finally, she received Bleomycin, Etoposide and Cisplatin (BEP) regimen in four courses and Vincristine, Actinomycin D (Dactinomycin) and Cyclophosphamide (VAC) regimen in two courses and Diphereline for saving the other ovary. Conclusion: Some young patients misinterpret the early symptoms of an ovarian neoplasm as those of pregnancy which can lead to a delay in the diagnosis. PMID:27141469

  6. Neutrophil Granulocytes in Ovarian Cancer - Induction of Epithelial-To-Mesenchymal-Transition and Tumor Cell Migration

    PubMed Central

    Mayer, Christine; Darb-Esfahani, Silvia; Meyer, Anne-Sophie; Hübner, Katrin; Rom, Joachim; Sohn, Christof; Braicu, Ioana; Sehouli, Jalid; Hänsch, G. Maria; Gaida, Matthias M.

    2016-01-01

    Background: Ovarian cancer (OvCa) is a highly aggressive malignoma with a tumor-promoting microenvironment. Infiltration of polymorphonuclear neutrophils (PMN) is frequently seen, raising the question of their impact on tumor development. In that context, effects of PMN on human ovarian cancer cells were assessed. Methods: Human epithelial ovarian cancer cells were incubated with human PMN, lysate of PMN, or neutrophil elastase. Morphological alterations were observed by time-lapse video-microscopy, and the underlying molecular mechanism was analyzed by flow cytometry and Western blotting. Functional alternations were assessed by an in vitro wound healing assay. In parallel, a large cohort of n=334 primary OvCa tissue samples of various histological subtypes was histologically evaluated. Results: Co-cultivation of cancer cells with either PMN or PMN lysate causes a change of the polygonal epithelial phenotype of the cells towards a spindle shaped morphology, causing a cribriform cell growth. The PMN-induced alteration could be attributed to elastase, a major protease of PMN. Elastase-induced shape change was most likely due to the degradation of membranous E-cadherin, which results in loss of cell contacts and polarity. Moreover, in response to elastase, epithelial cytokeratins were downmodulated, in parallel with a nuclear translocation of β-catenin. These PMN-elastase induced alterations of cells are compatible with an epithelial-to-mesenchymal transition (EMT) of the cancer cells. Following EMT, the cells displayed a more migratory phenotype. In human biopsies, neutrophil infiltration was seen in 72% of the cases. PMN infiltrates were detected preferentially in areas with low E-cadherin expression. Conclusion: PMN in the microenvironment of OvCa can alter tumor cells towards a mesenchymal and migratory phenotype. PMID:27053953

  7. Fluorescence-lifetime molecular imaging can detect invisible peritoneal ovarian tumors in bloody ascites

    PubMed Central

    Nakajima, Takahito; Sano, Kohei; Sato, Kazuhide; Watanabe, Rira; Harada, Toshiko; Hanaoka, Hirofumi; Choyke, Peter L; Kobayashi, Hisataka

    2014-01-01

    Blood contamination, such as bloody ascites or hemorrhages during surgery, is a potential hazard for clinical application of fluorescence imaging. In order to overcome this problem, we investigate if fluorescence-lifetime imaging helps to overcome this problem. Samples were prepared at concentrations ranging 0.3–2.4 μm and mixed with 0–10% of blood. Fluorescence intensities and lifetimes of samples were measured using a time-domain fluorescence imager. Ovarian cancer SHIN3 cells overexpressing the D-galactose receptor were injected into the peritoneal cavity 2.5 weeks before the experiments. Galactosyl serum albumin-rhodamine green (GSA-RhodG), which bound to the D-galactose receptor and was internalized thereafter, was administered intraperitoneally to peritoneal ovarian cancer-bearing mice with various degrees of bloody ascites. In vitro study showed a linear correlation between fluorescence intensity and probe concentration (r2 > 0.99), whereas the fluorescence lifetime was consistent (range, 3.33 ± 0.15–3.75 ± 0.04 ns). By adding 10% of blood to samples, fluorescence intensities decreased to <1%, while fluorescence lifetimes were consistent. In vivo fluorescence lifetime of GSA-RhodG stained tumors was longer than the autofluorescence lifetime (threshold, 2.87 ns). Tumor lesions under hemorrhagic peritonitis were not depicted using fluorescence intensity imaging; however, fluorescence-lifetime imaging clearly detected tumor lesions by prolonged lifetimes. In conclusion, fluorescence-lifetime imaging with GSA-RhodG depicted ovarian cancer lesions, which were invisible in intensity images, in hemorrhagic ascites. PMID:24479901

  8. Ovarian mucinous tumors arising from mature cystic teratomas--a molecular genetic approach for understanding the cellular origin.

    PubMed

    Fujii, Kaho; Yamashita, Yoriko; Yamamoto, Toshimichi; Takahashi, Koji; Hashimoto, Katsunori; Miyata, Tomoko; Kawai, Kumi; Kikkawa, Fumitaka; Toyokuni, Shinya; Nagasaka, Tetsuro

    2014-04-01

    Mucinous tumors of the ovary are frequently associated with mature cystic teratomas, and it has been speculated that the mucinous tumors arise from teratoma components. The cellular origins of mature cystic teratomas are believed to be post-meiotic ovarian germ cells, and the analysis of microsatellite markers such as short tandem repeats is suitable for determining the cellular origin of tumors. In this study, we analyzed 3 ovarian mature cystic teratomas, all of which were associated with simultaneous ovarian mucinous tumors within the same ovary. Two of the 3 mucinous tumors were intestinal-type and the other was endocervical type. A laser capture microdissection technique was used to separate the epithelial component of the mucinous tumor, the components of the mature cystic teratoma, and control ovarian somatic tissue. Using short tandem repeat analysis based on 6 markers (D20S480, D6S2439, D6S1056, D9S1118, D4S2639, and D17S1290), we could distinguish the germ cell (homozygous) or somatic (heterozygous) origin of a given component in each sample. The epithelial components of the intestinal-type mucinous tumors in cases 1 and 2 were homozygous, and the epithelial component in case 3 (endocervical type) was heterozygous. All teratomatous components were homozygous, and the control components were heterozygous. In addition, we analyzed 3 mature cystic teratomas without mucinous tumors, and all 3 were homozygous in the tumor component. Our data suggest that the origin of mucinous tumors in the ovary may differ among histological subtypes, and intestinal-type mucinous tumors may arise from mature cystic teratomas, although endocervical-type mucinous tumors may not. PMID:24485845

  9. Hotspot mutation panel testing reveals clonal evolution in a study of 265 paired primary and metastatic tumors

    PubMed Central

    Goswami, Rashmi S.; Patel, Keyur P.; Singh, Rajesh R.; Meric-Bernstam, Funda; Kopetz, E. Scott; Subbiah, Vivek; Alvarez, Ricardo H.; Davies, Michael A.; Jabbar, Kausar J.; Roy-Chowdhuri, Sinchita; Lazar, Alexander J.; Medeiros, L. Jeffrey; Broaddus, Russell R.; Luthra, Rajyalakshmi; Routbort, Mark J.

    2016-01-01

    Purpose We used a clinical next-generation sequencing hotspot mutation panel to investigate clonal evolution in paired primary and metastatic tumors. Experimental Design A total of 265 primary and metastatic tumor pairs were sequenced using a 46-gene cancer mutation panel capable of detecting one or more single nucleotide variants as well as small insertions/deletions. Mutations were tabulated together with tumor type and percentage, mutational variant frequency, time interval between onset of primary tumor and metastasis, and neoadjuvant therapy status. Results 227 of 265 (85.7%) tumor-metastasis pairs showed identical mutation calls. Of the tumor pairs with identical mutation calls, 160 (60.4%) possessed defining somatic mutation signatures and 67 (25.3%) did not exhibit any somatic mutations. There were 38 (14.3%) cases that showed at least one novel mutation call between the primary and metastasis. Metastases were almost two times more likely to show novel mutations (n=20, 7.5%) than primary tumors (n=12, 4.5%). TP53 was the most common additionally mutated gene in metastatic lesions, followed by PIK3CA and SMAD4. PIK3CA mutations were more often associated with metastasis in colon carcinoma samples. Conclusions Clinical next-generation sequencing hotspot panels can be useful in analyzing clonal evolution within tumors as well as in determining subclonal mutations that can expand in future metastases. PIK3CA, SMAD4 and TP53 are most often involved in clonal divergence, providing potential targets that may help guide the clinical management of tumor progression or metastases. PMID:25695693

  10. Analysis of potential response predictors to capecitabine/temozolomide in metastatic pancreatic neuroendocrine tumors.

    PubMed

    Cives, M; Ghayouri, M; Morse, B; Brelsford, M; Black, M; Rizzo, A; Meeker, A; Strosberg, J

    2016-09-01

    The capecitabine and temozolomide (CAPTEM) regimen is active in the treatment of metastatic pancreatic neuroendocrine tumors (pNETs), with response rates ranging from 30 to 70%. Small retrospective studies suggest that O(6)-methylguanine DNA methyltransferase (MGMT) deficiency predicts response to temozolomide. High tumor proliferative activity is also commonly perceived as a significant predictor of response to cytotoxic chemotherapy. It is unclear whether chromosomal instability (CIN), which correlates with alternative lengthening of telomeres (ALT), is a predictive factor. In this study, we evaluated 143 patients with advanced pNET who underwent treatment with CAPTEM for radiographic and biochemical response. MGMT expression (n=52), grade (n=128) and ALT activation (n=46) were investigated as potential predictive biomarkers. Treatment with CAPTEM was associated with an overall response rate (ORR) of 54% by RECIST 1.1. Response to CAPTEM was not influenced by MGMT expression, proliferative activity or ALT pathway activation. Based on these results, no biomarker-driven selection criteria for use of the CAPTEM regimen can be recommended at this time. PMID:27552969

  11. Exon-Level Transcriptome Profiling in Murine Breast Cancer Reveals Splicing Changes Specific to Tumors with Different Metastatic Abilities

    PubMed Central

    Bemmo, Amandine; Dias, Christel; Rose, April A. N.; Russo, Caterina; Siegel, Peter; Majewski, Jacek

    2010-01-01

    Background Breast cancer is the second most frequent type of cancer affecting women. We are increasingly aware that changes in mRNA splicing are associated with various characteristics of cancer. The most deadly aspect of cancer is metastasis, the process by which cancer spreads from the primary tumor to distant organs. However, little is known specifically about the involvement of alternative splicing in the formation of macroscopic metastases. Our study investigates transcript isoform changes that characterize tumors of different abilities to form growing metastases. Methods and Findings To identify alternative splicing events (ASEs) that are associated with the fully metastatic phenotype in breast cancer, we used Affymetrix Exon Microarrays to profile mRNA isoform variations genome-wide in weakly metastatic (168FARN and 4T07) and highly metastatic (4T1) mammary carcinomas. Statistical analysis identified significant expression changes in 7606 out of 155,994 (4%) exons and in 1725 out of 189,460 (1%) intronic regions, which affect 2623 out of 16,654 (16%) genes. These changes correspond to putative alternative isoforms—several of which are novel—that are differentially expressed between tumors of varying metastatic phenotypes. Gene pathway analysis showed that 1224 of genes expressing alternative isoforms were involved in cell growth, cell interactions, cell proliferation, cell migration and cell death and have been previously linked to cancers and genetic disorders. We chose ten predicted splice variants for RT-PCR validation, eight of which were successfully confirmed (MED24, MFI2, SRRT, CD44, CLK1 and HNRNPH1). These include three novel intron retentions in CD44, a gene in which isoform variations have been previously associated with the metastasis of several cancers. Conclusion Our findings reveal that various genes are differently spliced and/or expressed in association with the metastatic phenotype of tumor cells. Identification of metastasis

  12. α-Fetoprotein-producing ovarian tumor in a postmenopausal woman with germ cell differentiation.

    PubMed

    Meguro, Shiori; Yasuda, Masanori

    2013-02-01

    α-Fetoprotein (AFP)-producing ovarian tumors (APOTs) are rarely encountered in postmenopausal women, irrespective of whether they are of the germ cell or non-germ cell type. The APOTs that do occur in postmenopausal women are characterized by variable histologies such as hepatoid carcinoma, yolk sac tumor, and epithelial malignancies, most of which are combined. We herein present a case with APOT, which arose in a 58-year-old, gravida 2, para 2, postmenopausal woman. Preoperatively, the tumor, which was in the right ovary, was found to produce AFP (102768.0 ng/mL). The tumor was evenly composed of glands mimicking secretory endometrial gland or fetal gut accompanied by abundant stroma. Immunohistochemically, these glands were positive for SALL4, glypican-3, and hepatocyte nuclear factor 1β. We considered the present case as an AFP-producing adenocarcinoma with adenofibroma showing germ cell differentiation, but it seemed controversial that this tumor should be designated as a yolk sac tumor of the glandular type. The expression profiles of SALL4, OCT4, glypican-3, and hepatocyte nuclear factor 1β were thought to provide interesting implications to characterize the present case. PMID:22056036

  13. Downregulation of SASH1 correlates with tumor progression and poor prognosis in ovarian carcinoma

    PubMed Central

    REN, XIAOYAN; LIU, YIFEI; TAO, YUMEI; ZHU, GUOXIANG; PEI, MEILAN; ZHANG, JIANGUO; LIU, JIAN

    2016-01-01

    SAM- and SH3-domain containing 1 (SASH1) is a recently identified tumor suppressor gene that is required in the tumorigenesis of breast and other solid carcinomas. The SASH1 protein contains SH3 and SAM domains, indicating that it may serve an important role in intracellular signal transduction. The purpose of the present study was to investigate the expression of SASH1 in ovarian carcinoma and the correlation between its expression with clinical pathological features and clinical significance, and the effect of SASH1 on cell proliferation, apoptosis and migration of ovarian SKOV3 cells. The human ovarian carcinoma tissues and adjacent normal tissues were collected following surgery. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were used to detect the expression levels of SASH1 mRNA and protein, respectively. The expression levels of SASH1 mRNA and protein in ovarian carcinoma tissues were significantly lower than that observed in adjacent normal tissues (P<0.05). The expression levels of SASH1 in samples from patients without lymph nodes metastasis and patients with early FIGO stage was lower than those with lymph nodes metastasis and patients with advanced FIGO stage (P<0.05). Flow cytometry analysis and Transwell invasion chamber experiments were used to investigate the effect of SASH1 on the cell proliferation, apoptosis and migration of SKOV3 cells. The recombinant plasmid pcDNA3.1-SASH1 was constructed and transfected into SKOV3 cells. In addition, the SKOV3 cells in the pcDNA3.1-SASH1 group exhibited significantly reduced cell growth, proliferation, and migration ability compared to the empty vector group and normal group (P<0.01). There were a greater number of apoptotic cells in the pcDNA3.1-SASH1 group compared to the empty vector group and normal group (P<0.01). Taken together, these results indicated that SASH1 may be a tumor suppressor gene in ovarian carcinoma, and SASH1 expression inhibited growth

  14. Complete and Repeated Response of a Metastatic ALK-rearranged Inflammatory Myofibroblastic Tumor to Crizotinib in a Teenage Girl.

    PubMed

    Gaudichon, Jérémie; Jeanne-Pasquier, Corinne; Deparis, Marianna; Veyssière, Alexis; Heyndrickx, Maxime; Minckes, Odile; Orbach, Daniel

    2016-05-01

    Inflammatory myofibroblastic tumors (IMT) are rare tumors in children and young adults, considered by the World Health Organization to be intermediate malignancies and rarely metastasizing, with the presence of an anaplastic lymphoma kinase rearrangement in about 50% of the cases. We report the case of a teenager who presented with a metastatic aggressive IMT that was life-threatening despite multiple treatments, and which responded repeatedly to anaplastic lymphoma kinase-targeted crizotinib therapy. Crizotinib induced drastic primary tumor regression, which was sufficient to allow surgical resection and to control distant disease. This case shows that crizotinib is a promising therapy in IMT, even in adolescents and young adults. PMID:26808369

  15. Anti-ovarian tumor response of donor peripheral blood mononuclear cells is due to infiltrating cytotoxic NK cells

    PubMed Central

    Pandey, Veethika; Oyer, Jeremiah L.; Igarashi, Robert Y.; Gitto, Sarah B.; Copik, Alicja J.; Altomare, Deborah A.

    2016-01-01

    Treatment of ovarian cancer, a leading cause of gynecological malignancy, has good initial efficacy with surgery and platinum/taxane-based chemotherapy, but poor long-term survival in patients. Inferior long-term prognosis is attributed to intraperitoneal spreading, relapse and ineffective alternate therapies. Adoptive cell therapy is promising for tumor remission, although logistical concerns impede widespread implementation. In this study, healthy PBMCs were used to examine the immune response in a mouse model with human ovarian cancer, where natural killer (NK) cells were found to be the effector cells that elicited an anti-tumor response. Presence of tumor was found to stimulate NK cell expansion in mice treated intraperitoneally with PBMC+Interleukin-2 (IL-2), as compared to no expansion in non-tumor-bearing mice given the same treatment. PBMC+IL-2 treated mice exhibiting NK cell expansion had complete tumor remission. To validate NK cell mediated anti-tumor response, the intratumoral presence of NK cells and their cytotoxicity was confirmed by immunohistochemistry and granzyme activity of NK cells recovered from the tumor. Collectively, this study highlights the significance of NK cell-cytotoxic response to tumor, which may be attributed to interacting immune cell types in the PBMC population, as opposed to clinically used isolated NK cells showing lack of anti-tumor efficacy in ovarian cancer patients. PMID:26802025

  16. Nuclear β-arrestin1 is a critical cofactor of hypoxia-inducible factor-1α signaling in endothelin-1-induced ovarian tumor progression

    PubMed Central

    Rosanò, Laura; Caprara, Valentina; Sestito, Rosanna; Di Castro, Valeriana; Bagnato, Anna

    2016-01-01

    Hypoxia-inducible factor-1α (HIF-1α) mediates the response to hypoxia or other stimuli, such as growth factors, including endothelin-1 (ET-1), to promote malignant progression in numerous tumors. The importance of cofactors that regulate HIF-1α signalling within tumor is not well understood. Here we elucidate that ET-1/ETA receptor (ETAR)-induced pathway physically and functionally couples the scaffold protein β-arrestin1 (β-arr1) to HIF-1α signalling. In epithelial ovarian cancer (EOC) cells, ET-1/ETAR axis induced vascular-endothelial growth factor (VEGF) expression through HIF-1α nuclear accumulation. In these cells, activation of ETAR by ET-1, by mimicking hypoxia, promoted the nuclear interaction between β-arr1 and HIF-1α and the recruitment of p300 acetyltransferase to hypoxia response elements on the target gene promoters, resulting in enhanced histone acetylation, and HIF-1α target gene transcription. Indeed, β-arr1-HIF-1α interaction regulated the enhanced expression and release of downstream targets, such as ET-1 and VEGF, required for tumor cell invasion and pro-angiogenic effects in endothelial cells. These effects were abrogated by β-arr1 or HIF-1α silencing or by pharmacological treatment with the dual ET-1 receptor antagonist macitentan. Interestingly, ETAR/β-arr1 promoted the self-amplifying HIF-1α-mediated transcription of ET-1 that sustained a regulatory circuit involved in invasive and angiogenic behaviors. In a murine orthotopic model of metastatic human EOC, treatment with macitentan, or silencing of β-arr1, inhibits intravasation and metastasis formation. Collectively, these findings reveal the interplay of β-arr1 with HIF-1α in the complexity of ET-1/ETAR signalling, mediating epigenetic modifications directly involved in the metastatic process, and suggest that targeting ET-1-dependent β-arr1/HIF-1α pathway by using macitentan may impair EOC progression. PMID:26909598

  17. Surgical controversies in the management of post-chemotherapy nonretroperitoneal residual disease in metastatic nonseminomatous germ cell tumors

    PubMed Central

    Pandey, Durgatosh; Garg, Pankaj Kumar; Ray, Mukur Dipi; Mishra, Ashutosh

    2016-01-01

    Following the advent of platinum-based chemotherapy, Surgery, excepting orchidectomy, has become an adjunct treatment in the management of metastatic non-seminomatous germ cell tumors (NSGCT). Role of surgery comes into play in metastatic NSGCT when residual disease persists following standard chemotherapy. Surgical excision of all post chemotherapy residual disease at all places, whenever surgically feasible with acceptable morbidity and mortality, should be undertaken. As histopathological examination of the excised postchemotherapy residue shows only necrosis and fibrosis in significant number of patients; surgical exercise in this group of patients seems futile and unwarranted retrospectively. This issue becomes more contentious when surgeons are confronted with multiple nonretroperitoneal post chemotherapy residues. This article aims to deal with the management of postchemotherapy nonretroperitoneal residues in metastatic NSGCT. PMID:27169116

  18. Metastatic spread in patients with non-small cell lung cancer is associated with a reduced density of tumor-infiltrating T cells.

    PubMed

    Müller, Philipp; Rothschild, Sacha I; Arnold, Walter; Hirschmann, Petra; Horvath, Lukas; Bubendorf, Lukas; Savic, Spasenija; Zippelius, Alfred

    2016-01-01

    Tumor-infiltrating lymphocytes play an important role in cell-mediated immune destruction of cancer cells and tumor growth control. We investigated the heterogeneity of immune cell infiltrates between primary non-small cell lung carcinomas (NSCLC) and corresponding metastases. Formalin-fixed, paraffin-embedded primary tumors and corresponding metastases from 34 NSCLC patients were analyzed by immunohistochemistry for CD4, CD8, CD11c, CD68, CD163 and PD-L1. The percentage of positively stained cells within the stroma and tumor cell clusters was recorded and compared between primary tumors and metastases. We found significantly fewer CD4(+) and CD8(+) T cells within tumor cell clusters as compared with the stromal compartment, both in primary tumors and corresponding metastases. CD8(+) T cell counts were significantly lower in metastatic lesions than in the corresponding primary tumors, both in the stroma and the tumor cell islets. Of note, the CD8/CD4 ratio was significantly reduced in metastatic lesions compared with the corresponding primary tumors in tumor cell islets, but not in the stroma. We noted significantly fewer CD11c(+) cells and CD68(+) as well as CD163(+) macrophages in tumor cell islets compared with the tumor stroma, but no difference between primary and metastatic lesions. Furthermore, the CD8/CD68 ratio was higher in primary tumors than in the corresponding metastases. We demonstrate a differential pattern of immune cell infiltration in matched primary and metastatic NSCLC lesions, with a significantly lower density of CD8(+) T cells in metastatic lesions compared with the primary tumors. The lower CD8/CD4 and CD8/CD68 ratios observed in metastases indicate a rather tolerogenic and tumor-promoting microenvironment at the metastatic site. PMID:26541588

  19. Expression of c-myc and mutation of the KRAS gene in patients with ovarian mucinous tumors.

    PubMed

    Li, X S; Sun, J; He, X L

    2015-01-01

    We examined the expression of c-myc and mutations in the KRAS gene in ovarian mucinous tumors to explore the pathogenesis of these tumors and the feasibility of targeted gene therapy. Expression of c-myc protein and mutations in the KRAS gene in 24 cases of ovarian mucinous cystadenoma, 46 cases of ovarian borderline mucinous cystadenoma, and 46 cases of ovarian mucinous cystadenocarcinoma were detected using the immunohistochemistry PV-9000 2-step method and polymerase chain reaction-restriction fragment length polymorphism. The positive expression rates of c-myc in ovarian mucinous cystadenoma, borderline mucinous cystadenoma, and cystadenocarcinoma were 0, 39.1, and 65.2%, respectively (P < 0.01), while the mutation rates in KRAS were 0, 39.1 and 13.0%, respectively. The mutation rate of the borderline group was significantly higher, while rates in the other 2 groups were similar (P > 0.05). c-myc was not correlated with clinical stage, pathological grade, or age of patients with ovarian mucinous cystadenocarcinoma or borderline mucinous cystadenoma (P > 0.05), but was correlated with tumor size (P < 0.05). Mutations in KRAS were not correlated with clinical stage or tumor size in patients with borderline mucinous cystadenoma (P > 0.05), whereas it was correlated with age (P < 0.05). In borderline mucinous cystadenoma, c-myc expression and KRAS mutations were not correlated (P > 0.05). c-myc is involved in the formation of ovarian borderline mucinous cystadenoma and mucinous cystadenocarcinoma, and the KRAS gene may contribute to the formation of borderline mucinous cystadenoma. PMID:26400304

  20. Papillary thyroid carcinoma with extensive squamous dedifferentiation metastatic to the lung: BRAF mutational analysis as a useful tool to rule out tumor to tumor metastasis.

    PubMed

    Acosta, Andres M; Pins, Michael R

    2016-02-01

    Tumors containing elements of both papillary thyroid carcinoma (PTC) and squamous cell carcinoma (SCC) are rare but well documented. When they present initially as metastatic disease in an organ that can harbor a primary SCC, the possibility of a tumor to tumor metastasis (TTM) must be considered. The aim of this case study is to illustrate how BRAF mutational analysis can be used to help differentiate between these two diagnoses. We report a 63-year-old male with a longstanding history of PTC metastatic to the brain and lymph nodes who presented to our institution with a right lower lobe lung mass after a 2-year recurrence-free interval. Histopathologic and immunohistochemical analysis revealed a composite neoplasm with distinct elements of both PTC and SCC. We performed BRAF (V600E) (c.1799 T > A) mutational analysis to help elucidate the origin of each component. This is the first time that BRAF sequencing has been used to discriminate between dedifferentiated PTC and TTM, to the best of our knowledge. In the context of metastatic PTC with SCC dedifferentiation, the presence of the identical BRAF (V600E) (c.1799 T > A) mutation in both components might help rule out tumor to tumor metastasis. PMID:26521063

  1. Tumor and Plasma Met Levels in Non-Metastatic Prostate Cancer

    PubMed Central

    Kaye, Deborah R.; Pinto, Peter A.; Cecchi, Fabiola; Reilly, Joseph; Semerjian, Alice; Rabe, Daniel C.; Gupta, Gopal; Choyke, Peter L.

    2016-01-01

    Objective To measure Met protein content in prostate biopsies guided by fused magnetic resonance and ultrasound imaging, and to measure soluble Met (sMet) protein concentration in plasma samples from patients presenting evidence of prostate cancer. Patients and Methods 345 patients had plasma samples drawn prior to image-guided biopsy of the prostate. Of these, 32% had benign biopsies. Of the 236 that were positive for prostate adenocarcinoma (PCa), 132 treated by total prostatectomy had Gleason scores of 6 (17%), 7, (55%), 8 (16%), or 9–10 (12%). 23% had evidence of local invasion. Plasma samples were also obtained from 80 healthy volunteers. Tissue Met and plasma sMet were measured by two-site immunoassay; values were compared among clinically defined groups using non-parametric statistical tests to determine significant differences or correlations. Results PCa tumor Met correlated significantly with plasma sMet, but median values were similar among benign and malignant groups. Median plasma sMet values were also similar among those groups, although both medians were significantly above normal. Median Met content in primary PCa tumors and sMet concentrations were independent of Gleason score, final pathologic stage and age. Conclusion Plasma sMet is not predictive of PCa or its severity in patients with organ-confined or locally invasive disease. Quantitative analysis of Met protein content and activation state in PCa tumor biopsy samples was highly feasible and may have value in follow-up to genomic and/or transcriptomic-based screens that show evidence of oncogenically relevant MET gene features that occur at relatively low frequency in non-metastatic PCa. PMID:27300295

  2. Can PPH3 be helpful to assess the discordant grade in primary and metastatic enteropancreatic neuroendocrine tumors?

    PubMed

    Dumars, Clotilde; Foubert, Fanny; Touchefeu, Yann; Regenet, Nicolas; Senellart, Hélène; Matysiak-Budnik, Tamara; Heymann, Marie-Françoise

    2016-08-01

    Therapeutic strategy in neuroendocrine tumors (NETs) is based on histological characteristics of the primary tumor (PT), even in case of metastatic disease. Our aim was to compare the tumor grade between PT and their liver metastases (LM) in patients with enteropancreatic NETs. Forty-one patients treated for sporadic NETs (10 pancreatic, 31 intestinal) were included. All presented synchronous (35) or metachronous (6) LM. Tumor grade was evaluated for PT and LM according to the WHO classification, using Ki-67 labeling and mitotic count (MC) evaluated with or without phospho-histone H3 (PPH3). Tumor grade differed between primary and metastatic tumor in 16/41 patients (39 %), with an increase of grade in 13 of them (32 %). The median Ki-67, MC, and PPH3 in metastases were statistically higher than in PT (p = 0.0002, 0.02, and 0.01). In 17 of 65 cases tested with PPH3 (26 %), this antibody was more efficient in assessing the grade compared to the usual MC, and in 2/65 cases compared to the Ki-67. A better correlation was observed between Ki-67 and PPH3 (p = 0.0001) than between Ki-67 and MC without immunohistochemistry. There is a significant difference in tumor grade between primary and metastatic NETs, underlining the necessity of a systematic biopsy on LM for patient management. Moreover, PPH3 appears to be a powerful antibody to assess the MC and the tumor grade much more accurately when associated with Ki-67. PMID:27048356

  3. Multiple hepatic sclerosing hemangioma mimicking metastatic liver tumor successfully treated by laparoscopic surgery: Report of a case

    PubMed Central

    Wakasugi, Masaki; Ueshima, Shigeyuki; Tei, Mitsuyoshi; Tori, Masayuki; Yoshida, Ken-ichi; Tsujimoto, Masahiko; Akamatsu, Hiroki

    2015-01-01

    Introduction Hepatic sclerosing hemangioma is a very rare benign tumor, characterized by fibrosis and hyalinization occurring in association with degeneration of a hepatic cavernous hemangioma. We report here a rare case of multiple hepatic sclerosing hemangioma mimicking metastatic liver tumor that was successfully treated using laparoscopic surgery. Presentation of case A 67-year-old woman with multiple liver tumors underwent single-incision laparoscopic sigmoidectomy under a diagnosis of advanced sigmoid cancer with multiple liver metastases. Examination of surgical specimens of sigmoid colon revealed moderately differentiated adenocarcinoma invading the serosa, and no lymph node metastases. Serum levels of carcinoembryonic antigen and carbohydrate antigen 19-9 remained within normal limits throughout the course. Two months after sigmoidectomy, the patient underwent laparoscopic partial hepatectomy of S1 and S6 of the liver and cholecystectomy. Histopathological examination showed that the tumors mainly comprised hyalinized tissue and collagen fibers with sporadic vascular spaces on hematoxylin and eosin-stained sections, yielding a diagnosis of multiple hepatic sclerosing hemangioma. No evidence of recurrence has been seen as of 21 months postoperatively. Discussion Differentiating multiple sclerosing hemangiomas from metastatic liver tumors was quite difficult because the radiological findings were closely compatible with liver metastases. Laroscopic hepatectomy provided less blood loss, a shorter duration of hospitalization, and good cosmetic results. Conclusion Sclerosing hemangioma should be included among the differential diagnoses of multiple liver tumors in patients with colorectal cancer. Laparoscopic hepatectomy is useful for diagnostic therapy for undiagnosed multiple liver tumors. PMID:25679307

  4. Anti-tumor activity and the mechanism of SIP-S: A sulfated polysaccharide with anti-metastatic effect.

    PubMed

    Zong, Aizhen; Liu, Yuhong; Zhang, Yan; Song, Xinlei; Shi, Yikang; Cao, Hongzhi; Liu, Chunhui; Cheng, Yanna; Jiang, Wenjie; Du, Fangling; Wang, Fengshan

    2015-09-20

    Our previous studies demonstrated that SIP-S had anti-metastatic activity and inhibited the growth of metastatic foci. Here we report the anti-tumor and immunoregulatory potential of SIP-S. SIP-S could significantly inhibit tumor growth in S180-bearing mice, and the inhibition rates was 43.7% at 30 mg/kg d. Besides, SIP-S could improve the thymus and spleen indices of S180-bearing mice and the mice treated with CTX. The combination of SIP-S (15 mg/kg d) with CTX (12.5 mg/kg d) showed higher anti-tumor potency than CTX (25 mg/kg d) alone. These results indicated that SIP-S had immunoenhancing and anticancer activity, and the immunoenhancing activity might be one mechanism for its anti-tumor activity. Flow cytometry results showed that SIP-S could induce tumor cells apoptosis. Western blot analysis indicated that SIP-S could upregulate the expression of pro-apoptotic proteins, caspase-3, -8, -9 and Bax, and downregulate the expression of anti-apoptotic protein PARP-1 in tumor cells in a dose-dependent manner. In summary, SIP-S has anti-tumor activity, which may be associated with its immunostimulating and pro-apoptotic activity. PMID:26050887

  5. [Early diagnosis of metastatic spinal tumor is a key for effective palliative radiotherapy in patients with lung cancer].

    PubMed

    Isono, Hisayo; Kemmoku, Tomoko; Nakamura, Yusuke; Onose, Akira; Matsumoto, Yuka; Watanabe, Rinako; Haraguchi, Mizuha; Kasajima, Masashi; Takaya, Saho; Ishihara, Mikiko; Karigane, Daiki; Nagata, Hiroshi

    2011-12-01

    Patients with metastatic spinal tumor are the largest in number among the patients with bone tumor. It causes a severe bone pain, pathological fracture and spinal cord compression. Thus it harshly hampers patient's quality of life. We report 3 patients with lung cancer whose initial manifestation was metastatic spinal tumor. We treated the 3 patients with palliative radiotherapy and medication. Although the severe pain has improved on a numerical rating scale(NRS), but performance status(PS)and activity of daily living(ADL)of the 3 patients got worse because the disease was progressed and complicated. Generally, PS of cancer patients found by bone matastasis is low. However, it is difficult to take an effective treatment, which leads to ADL improvement. There are many choices for treating metastatic bone tumors including pain control, bisphosphonate administration, radiation therapy, strontium radiotherapy, bone cement, palliative surgery and orthotics. In addition, a development of molecular target drugs, such as Denosmab, is expected as future modality of palliative care. In conclusion, we should detect a bone metastasis in the patient with lung cancer as early as possible, and select an appropriate treatment in collaboration with each specialist for achieving the ADL and PS improvement. PMID:22189323

  6. Primary tumor prevalence has an impact on the constituent ratio of metastases to the jaw but not on metastatic sites

    PubMed Central

    Zhang, Fu-gui; Hua, Cheng-ge; Shen, Mo-lun; Tang, Xiu-fa

    2011-01-01

    This article provides an overview of metastases to jaws (MJ), mainly concerning the differences between American and Chinese patients, and exploring the relationship between the primary tumors' prevalence (PTP) and constituent ratio of MJ. Information concerning of 399 MJ cases in 215 papers, including one new case in our hospital, was subjected to statistic analysis. The main clinical features of MJ, such as constituent ratio of PTP and that of MJ, metastatic sites, treatments, and prognosis were summarized. Breast, lung, kidney, prostate and thyroid (in descending order) were the leading primary sites of MJ. Furthermore, the constituent ratio of MJ was found to be correlated with that of PTP in all subjects including American and Chinese subjects in our study. As to metastatic sites in the mandible, a specific “M” shaped pattern appeared regardless of the tumor type or constituent ratios of MJ were in all subjects. Almost all subjects received traditionally palliative treatments, and the prognosis was quite poor. The PTP had a significant impact on the constituent ratio of MJ. However, it was the properties of the microenvironment rather than characteristics or constituent ratios of tumor cells, that decided the metastatic sites in various tumor subjects. PMID:21789963

  7. Advances in Tumor Screening, Imaging, and Avatar Technologies for High-Grade Serous Ovarian Cancer

    PubMed Central

    Ohman, Anders W.; Hasan, Noor; Dinulescu, Daniela M.

    2014-01-01

    The majority of high-grade serous ovarian carcinoma cases are detected in advanced stages when treatment options are limited. Surgery is less effective at eradicating the disease when it is widespread, resulting in high rates of disease relapse and chemoresistance. Current screening techniques are ineffective for early tumor detection and consequently, BRCA mutations carriers, with an increased risk for developing high-grade serous ovarian cancer, elect to undergo risk-reducing surgery. While prophylactic surgery is associated with a significant reduction in the risk of cancer development, it also results in surgical menopause and significant adverse side effects. The development of efficient early-stage screening protocols and imaging technologies is critical to improving the outcome and quality of life for current patients and women at increased risk. In addition, more accurate animal models are necessary in order to provide relevant in vivo testing systems and advance our understanding of the disease origin and progression. Moreover, both genetically engineered and tumor xenograft animal models enable the preclinical testing of novel imaging techniques and molecularly targeted therapies as they become available. Recent advances in xenograft technologies have made possible the creation of avatar mice, personalized tumorgrafts, which can be used as therapy testing surrogates for individual patients prior to or during treatment. High-grade serous ovarian cancer may be an ideal candidate for use with avatar models based on key characteristics of the tumorgraft platform. This review explores multiple strategies, including novel imaging and screening technologies in both patients and animal models, aimed at detecting cancer in the early-stages and improving the disease prognosis. PMID:25478323

  8. Protease activated receptor-1 inhibits the Maspin tumor-suppressor gene to determine the melanoma metastatic phenotype

    PubMed Central

    Villares, Gabriel J.; Zigler, Maya; Dobroff, Andrey S.; Wang, Hua; Song, Renduo; Melnikova, Vladislava O.; Huang, Li; Braeuer, Russell R.; Bar-Eli, Menashe

    2011-01-01

    The thrombin receptor protease activated receptor-1 (PAR-1) is overexpressed in metastatic melanoma cell lines and tumor specimens. Previously, we demonstrated a significant reduction in tumor growth and experimental lung metastasis after PAR-1 silencing via systemic delivery of siRNA encapsulated into nanoliposomes. Gene expression profiling identified a 40-fold increase in expression of Maspin in PAR-1–silenced metastatic melanoma cell lines. Maspin promoter activity was significantly increased after PAR-1 silencing, suggesting that PAR1 negatively regulates Maspin at the transcriptional level. ChIP analyses revealed that PAR-1 decreases binding of Ets-1 and c-Jun transcription factors to the Maspin promoter, both known to activate Maspin transcription. PAR-1 silencing did not affect Ets-1 or c-Jun expression; rather it resulted in increased expression of the chromatin remodeling complex CBP/p300, as well as decreased activity of the CBP/p300 inhibitor p38, resulting in increased binding of Ets-1 and c-Jun to the Maspin promoter and higher Maspin expression. Functionally, Maspin expression reduced the invasive capability of melanoma cells after PAR-1 silencing, which was abrogated after rescuing with PAR-1. Furthermore, tumor growth and experimental lung metastasis was significantly decreased after expressing Maspin in a metastatic melanoma cell line. Moreover, silencing Maspin in PAR-1–silenced cells reverted the inhibition of tumor growth and experimental lung metastasis. Herein, we demonstrate a mechanism by which PAR-1 negatively regulates the expression of the Maspin tumor-suppressor gene in the acquisition of the metastatic melanoma phenotype, thus attributing an alternative function to PAR-1 other than coagulation. PMID:21187389

  9. Protease activated receptor-1 inhibits the Maspin tumor-suppressor gene to determine the melanoma metastatic phenotype.

    PubMed

    Villares, Gabriel J; Zigler, Maya; Dobroff, Andrey S; Wang, Hua; Song, Renduo; Melnikova, Vladislava O; Huang, Li; Braeuer, Russell R; Bar-Eli, Menashe

    2011-01-11

    The thrombin receptor protease activated receptor-1 (PAR-1) is overexpressed in metastatic melanoma cell lines and tumor specimens. Previously, we demonstrated a significant reduction in tumor growth and experimental lung metastasis after PAR-1 silencing via systemic delivery of siRNA encapsulated into nanoliposomes. Gene expression profiling identified a 40-fold increase in expression of Maspin in PAR-1-silenced metastatic melanoma cell lines. Maspin promoter activity was significantly increased after PAR-1 silencing, suggesting that PAR1 negatively regulates Maspin at the transcriptional level. ChIP analyses revealed that PAR-1 decreases binding of Ets-1 and c-Jun transcription factors to the Maspin promoter, both known to activate Maspin transcription. PAR-1 silencing did not affect Ets-1 or c-Jun expression; rather it resulted in increased expression of the chromatin remodeling complex CBP/p300, as well as decreased activity of the CBP/p300 inhibitor p38, resulting in increased binding of Ets-1 and c-Jun to the Maspin promoter and higher Maspin expression. Functionally, Maspin expression reduced the invasive capability of melanoma cells after PAR-1 silencing, which was abrogated after rescuing with PAR-1. Furthermore, tumor growth and experimental lung metastasis was significantly decreased after expressing Maspin in a metastatic melanoma cell line. Moreover, silencing Maspin in PAR-1-silenced cells reverted the inhibition of tumor growth and experimental lung metastasis. Herein, we demonstrate a mechanism by which PAR-1 negatively regulates the expression of the Maspin tumor-suppressor gene in the acquisition of the metastatic melanoma phenotype, thus attributing an alternative function to PAR-1 other than coagulation. PMID:21187389

  10. Effect of preemptive analgesia with intravenous oxycodone in the patients undergoing laparoscopic resection of ovarian tumor

    PubMed Central

    Wang, Na; Wang, Yuantao; Pang, Lei; Wang, Jinguo

    2015-01-01

    Objective: To evaluate the efficacy of preemptive intravenous oxycodone in the patients undergoing laparoscopic resection of ovarian tumor. Methods: Sixty ASA I or II patients undergoing elective laparoscopic resection of ovarian tumor were randomly allocated to one of two groups: Group O (n=30) received intravenous oxycodone (0.1 mg·kg-1) 10 minutes before surgery over 2 minutes, and Group N (n=30) received an equivalent volume of normal saline. All patients received a standardized general anesthesia. MBP and HR at the time of arrival of the operating room (T1), 5 min before pneumoperitoneum (T2), 5 minutes (T3), 10 minutes (T4), and 15 minutes after pneumoperitoneum (T5), and VAS scores at postoperative 2, 4, 8, 12 and 24 hour were recorded. The tramadol consumption and side effects in 24 h after surgery were recorded. Results: VAS pain scores at 2, 4, 8 and 12 hour after operation were significantly lower in Group O (P<0.05). MBP and HR increased significantly due to pneumoperitoneum at T3, T4 and T5, compared with T1 and T2 within Group N, and were higher at T3, T4 and T5 in Group N than at the same time points in Group O. Tramadol consumption was statistically lower in Group O (P=0.0003). Conclusions: Preemptive intravenous oxycodone was an efficient and safe method to reduce intraoperative haemodynamic effect and postoperative pain. PMID:26101479

  11. Acetyl-L-Carnitine Hydrochloride in Preventing Peripheral Neuropathy in Patients With Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cavity Cancer, or Fallopian Tube Cancer Undergoing Chemotherapy

    ClinicalTrials.gov

    2014-12-29

    Fatigue; Malignant Ovarian Mixed Epithelial Tumor; Neuropathy; Neurotoxicity Syndrome; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Pain; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma

  12. Prognostic Significance of the Tumor-Stroma Ratio in Epithelial Ovarian Cancer

    PubMed Central

    Chen, Ying; Zhang, Lei; Liu, Wenxin; Liu, Xiangyu

    2015-01-01

    Tumor-stroma ratio (TSR) has recently been identified as a promising prognostic parameter for several solid tumors. This study aimed to evaluate the prognostic role of TSR in epithelial ovarian cancer (EOC) and 838 EOC patients were enrolled in this study. TSR was estimated on hematoxylin-and-eosin-stained tissue sections from the most invasive part of the primary tumor. Patients were classified as stroma-rich or stroma-poor according to the proportion of stroma ≥50% or <50%. Chi-square test analysis revealed that TSR were significantly associated with FIGO stage, LN status, and recurrence or not (all of them P < 0.001). The higher stroma-rich proportions were found in EOC patients with advanced stage (36.13% versus 19.75%), LN metastasis (51.93% versus 27.25%), and recurrence (34.27% versus 6.82%). Stroma-rich EOC patients had obvious shorter median time of progression-free survival (29 versus 39 months) and overall survival (50 versus 58 months), respectively. TSR was an independent prognostic factor for the evaluation of PFS in EOC. Stroma-rich tumors had worse prognosis and higher risk of relapse compared with those in stroma-poor tumors in EOC patients. Considered easy to determine for routine pathological examination, TSR may serve as a new prognostic histological parameter in EOC. PMID:26609529

  13. Feto-maternal outcomes of pregnancy complicated by ovarian sex-cord stromal tumor: a systematic review of literature.

    PubMed

    Blake, Erin A; Carter, Charelle M; Kashani, Banafsheh N; Kodama, Michiko; Mabuchi, Seiji; Yoshino, Kiyoshi; Matsuo, Koji

    2014-04-01

    Sex-cord stromal tumors (SCSTs) are rare ovarian cancers and their behavior during pregnancy is not well understood. To evaluate the maternal and fetal outcomes of pregnancy complicated by ovarian SCST, a systematic literature search was conducted in PubMed/MEDLINE using entry key words "pregnancy" and each type of ovarian SCST ("sex cord stromal tumor," "granulosa cell tumor," "thecoma," "Sertoli-Leydig cell tumor," or "gynandroblastoma") between 1955 and 2012 that identified 46 cases eligible for the analysis. Clinical characteristics, pregnancy outcome, tumor characteristics, and survival outcomes were evaluated. Serious adverse events were defined as complications related to the SCST that resulted in severe morbidity or mortality for mother, fetus, or both. The most common histology was granulosa cell tumor (22.0%), followed by thecoma (18.6%) and Sertoli-Leydig cell tumor (8.5%). Abdomino-pelvic pain (45.7%), palpable mass (30.4%), and virilization (26.1%) were the three most common symptoms. The majority were stage I (76.1%), tumor size <15cm (64.9%), and underwent unilateral adnexectomy (80.4%). Fetal conservation surgery was seen in 54.3%. Most cases had live births (78.3%) at full term (60.9%). Among cases proceeded expectant delay of delivery (45.7%), most cases resulted in live birth (95.2%) with median expectant interval of 20.7 weeks. Maternal and/or fetal serious adverse events (SAEs) were observed in 41.3% with maternal shock/hemoperitoneum being the most common complication (13.0%). Logistic regression test identified younger age (<30 versus ≥30, 73.3% versus 26.7%, odds ratio [OR] 11.7, 95%CI 1.35-101, p=0.026), large tumor (size ≥15cm versus <15cm, 64.9% versus 35.1%, OR 10.0, 95%CI 1.29-26.2, p=0.004), and advanced-stage (stages II-IV versus I, 76.1% versus 23.9%, OR 5.82, 95%CI 2.05-48.9, p=0.022) as risk factors of increased SAE. Overall survival of patients diagnosed with ovarian SCST during pregnancy was comparable to ovarian SCST not

  14. Mixed ovarian germ cell tumor composed of immature teratoma, yolk sac tumor and embryonal carcinoma.

    PubMed

    Wang, Ying; Zhou, Feng; Qian, Zhida; Qing, Jiale; Zhao, Mengdam; Huang, Lili

    2014-11-01

    We report the case of a 19-year-old woman experiencing lower abdominal distension and pain. Laboratory tests indicated elevated serum levels of Alpha-Fetoprotein (AFP) and human Chorionic Gonadotropin (hCG). A large mass was detected in the abdomen by physical examination and by transvaginal ultrasonography. Exploratory laparotomy was performed, and a smooth-surfaced, spherical, solid tumor was found on the left ovary, measuring 11.5 x 9.9 x 6.9 cm. Histological evaluation revealed that the tumor consisted of a combination of immature teratoma, Yolk Sac Tumor, and embryonal carcinoma; this is a very rare combination in mixed germ cell tumors. PMID:25518772

  15. Unusual Sertoli Cell Tumor Associated With Sex Cord Tumor With Annular Tubules in Peutz-Jeghers Syndrome: Report of a Case and Review of the Literature on Ovarian Tumors in Peutz-Jeghers Syndrome.

    PubMed

    Ravishankar, Sanjita; Mangray, Shamlal; Kurkchubasche, Arlet; Yakirevich, Evgeny; Young, Robert H

    2016-05-01

    We report the case of an 11-year-old girl with Peutz-Jeghers syndrome and a unilateral ovarian tumor most consistent with Sertoli cell tumor associated with sex cord tumor with annular tubules. The ovary was replaced by a lobular, solid, yellow tumor. Microscopic examination showed 2 components that focally merged. The first was composed of uniform, cytologically bland cells arranged mostly in diffuse sheets and focally in tubules. The second showed typical sex cord tumor with annular tubules with extensive calcification. The predominant component of the tumor clearly fell in the sex cord category and most closely resembled Sertoli cell tumor. This case adds to the limited information on ovarian sex cord tumors, other than typical sex cord tumor with annular tubules, arising in association with Peutz-Jeghers syndrome, a topic reviewed herein. PMID:26621753

  16. Paclitaxel, Cisplatin, and Topotecan With or Without Filgrastim in Treating Patients With Newly Diagnosed Stage III or Stage IV Epithelial Ovarian Cancer

    ClinicalTrials.gov

    2013-01-23

    Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Stage III Ovarian Epithelial Cancer; Stage IV Ovarian Epithelial Cancer

  17. TLR4 activates NF-{kappa}B in human ovarian granulosa tumor cells

    SciTech Connect

    Woods, Dori C.; Johnson, A.L.

    2011-06-17

    Highlights: {yields} TLR4 is expressed in human ovarian granulosa tumor cells. {yields} Acting through TLR4, LPS and HSP60 induce a NF{kappa}B signaling cascade in human ovarian granulosa tumor cells. {yields} NF{kappa}B activation or inhibition did not alter chemosensitivity to TRAIL or cisplatin. -- Abstract: Previous studies have demonstrated expression of Toll-like receptors (TLRs) in the surface epithelium of normal ovaries (OSE) and in epithelial ovarian tumors. Most notably, OSE-derived cancers express TLR4, which activates the nuclear factor-kappa B (NF-{kappa}B) signaling cascade as a mediator of inflammatory response. Currently, there is considerable interest in elucidating the role of TLR-mediated signaling in cancers. Nevertheless, the expression of TLRs in granulosa cell tumors (GCTs) of the ovary, and the extent to which GCT expression of TLRs may influence cell-signaling pathways and/or modulate the efficacy of chemotherapeutics, has yet to be determined. In the present study, human GCT lines (COV434 and KGN) were utilized to evaluate expression of functional TLR4. TLR4 is expressed in GCT cell lines and ligation of TLR4 with bacterial lipopolysaccharide (LPS) led to I{kappa}B degradation and activation of NF-{kappa}B. NF-{kappa}B activation was confirmed by nuclear localization of NF-{kappa}B p65 following treatment with LPS and the naturally occurring ligand, HSP60. Notably, immunoneutralization of TLR4 blocked nuclear localization, and inhibition of NF-{kappa}B signaling attenuated LPS-induced TNF{alpha} plus increased doubling time in both cell lines. Contradictory to reports using human OSE cell lines, inhibition of NF-{kappa}B signaling failed to sensitize GCT lines to TRAIL or cisplatin. In summary, findings herein are the first to demonstrate a functional TLR-signaling pathway specifically in GCTs, and indicate that in contrast to OSE-derived cancers, inhibition of NF-{kappa}B does not sensitize GCTs to TRAIL or cisplatin.

  18. Appropriateness of systemic treatments in unresectable metastatic well-differentiated pancreatic neuroendocrine tumors

    PubMed Central

    Strosberg, Jonathan R; Fisher, George A; Benson, Al B; Anthony, Lowell B; Arslan, Bulent; Gibbs, John F; Greeno, Edward; Iyer, Renuka V; Kim, Michelle K; Maples, William J; Philip, Philip A; Wolin, Edward M; Cherepanov, Dasha; Broder, Michael S

    2015-01-01

    AIM: To evaluate systemic treatment choices in unresectable metastatic well-differentiated pancreatic neuroendocrine tumors (PNETs) and provide consensus treatment recommendations. METHODS: Systemic treatment options for pancreatic neuroendocrine tumors have expanded in recent years to include somatostatin analogs, angiogenesis inhibitors, inhibitors of mammalian target of rapamycin and cytotoxic agents. At this time, there is little data to guide treatment selection and sequence. We therefore assembled a panel of expert physicians to evaluate systemic treatment choices and provide consensus treatment recommendations. Treatment appropriateness ratings were collected using the RAND/UCLA modified Delphi process. After studying the literature, a multidisciplinary panel of 10 physicians assessed the appropriateness of various medical treatment scenarios on a 1-9 scale. Ratings were done both before and after an extended discussion of the evidence. Quantitative measurements of agreement were made and consensus statements developed from the second round ratings. RESULTS: Specialties represented were medical and surgical oncology, interventional radiology, and gastroenterology. Panelists had practiced for a mean of 15.5 years (range: 6-33). Among 202 rated scenarios, disagreement decreased from 13.2% (26 scenarios) before the face-to-face discussion of evidence to 1% (2) after. In the final ratings, 46.5% (94 scenarios) were rated inappropriate, 21.8% (44) were uncertain, and 30.7% (62) were appropriate. Consensus statements from the scenarios included: (1) it is appropriate to use somatostatin analogs as first line therapy in patients with hormonally functional tumors and may be appropriate in patients who are asymptomatic; (2) it is appropriate to use everolimus, sunitinib, or cytotoxic chemotherapy therapy as first line therapy in patients with symptomatic or progressive tumors; and (3) beyond first line, these same agents can be used. In patients with uncontrolled

  19. Eribulin Mesylate and Gemcitabine Hydrochloride in Treating Patients With Metastatic Solid Tumors or Solid Tumors That Cannot be Removed by Surgery

    ClinicalTrials.gov

    2016-04-05

    Adult Solid Neoplasm; Recurrent Ovarian Carcinoma; Recurrent Uterine Corpus Carcinoma; Stage III Ovarian Cancer; Stage III Uterine Corpus Cancer; Stage IV Ovarian Cancer; Stage IV Uterine Corpus Cancer

  20. In vitro production of cyclic AMP and steroids from an ovarian Sertoli-Leydig cell tumor. Notes on clinical management.

    PubMed

    Abrahamsson, G; Dahlgren, E; Hahlin, M; Knutson, F; Norström, A; Janson, P O

    1995-04-01

    A 27 year old nulliparous woman with a history of chronic anovulation and signs of virilization with a markedly elevated serum level of testosterone, underwent a laparotomy with peroperative bilateral ovarian vein catheterization and bilateral bisection of both ovaries. A solid, 1.5 cm, well delimited tumor located centrally in the right ovary, was excised. Testosterone levels in ovarian venous blood from the tumor bearing side, were 88.4 nmol/l and from the contralateral ovary 3.9 nmol/l. Histopathological examination showed a Sertoli-Leydig cell tumor which was radically extirpated. Postoperatively, the serum levels of androgen normalized, the woman had regular cycles, became pregnant and delivered a normal female baby. Pieces of tumor tissue were incubated for 2 h, with and without addition of gonadotropins and adrenocorticotropic hormone (ACTH). Human chorionic gonadotropin (CG), follicle stimulating hormone (FSH) and adrenocorticotropic hormone (ACTH) caused significant increases in cyclic monophosphate (cAMP) production in tumor tissue in vitro, as compared to controls. Furthermore, ACTH also significantly stimulated 17 beta-estradiol production. In tumor cells cultured for 48 h, FSH slightly, but not significantly, increased the production of progesterone. In the cell culture, [3H]-thymidine incorporation into deoxyribonucleic acid (DNA) was stimulated by IGF1 alpha but not by hCG and FSH. It is concluded that Sertoli-Leydig cell tumors may be sensitive to gonadotropins and ACTH and that their small size, solid shape and intra-ovarian localization can cause diagnostic difficulties. PMID:7732806

  1. Survival Outcomes and Tumor IMP3 Expression in Patients with Sarcomatoid Metastatic Renal Cell Carcinoma

    PubMed Central

    Tantravahi, Srinivas K.; Albertson, Daniel; Agarwal, Archana M.; Poole, Austin; Patel, Shiven B.; Hawatmeh, Jamil S.; Straubhar, Alli M.; Liu, Ting; Stenehjem, David D.

    2015-01-01

    Metastatic renal cell carcinoma with sarcomatoid histology (SmRCC) is associated with poor survival. No data is available from randomized trials on the efficacy of vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) inhibitors in SmRCC. We identified SmRCC patients from a single institutional database. To identify predictive and prognostic biomarkers, immunohistochemistry (IHC) analysis was performed on the tumor samples for downstream targets of VEGF and mTOR pathways. Survival outcomes were stratified by IHC analysis, extent of sarcomatoid component, Memorial Sloan-Kettering Cancer Center (MSKCC), and Heng risk criteria. Twenty-seven patients with SmRCC were included. First line therapy included targeted therapy (n = 19), immunotherapy (n = 4), cytotoxic chemotherapy (n = 1), and no treatment (n = 3). Median OS was 8.2 months (95% CI 3.8–14.2 months). Median survival in months, based on MSKCC and Heng risk groups, was favorable 89.3 versus 84.5, intermediate 9.5 versus 12.7, and poor 3.9 versus 5.1. None of the IHC markers predicted outcomes of treatment with VEGF or mTOR inhibitors. Only tumor IMP3 expression was associated with inferior OS, although not statistically significant (IMP3 negative 14.2 versus IMP3 positive 4.9 months; HR 0.46, 95% CI 0.16–1.21; P = 0.12). The study was limited by small sample size. PMID:25688268

  2. Morphological and Immunohistochemical Reevaluation of Tumors Initially Diagnosed as Ovarian Endometrioid Carcinoma With Emphasis on High-grade Tumors.

    PubMed

    Lim, Diana; Murali, Rajmohan; Murray, Melissa P; Veras, Emanuela; Park, Kay J; Soslow, Robert A

    2016-03-01

    Ovarian endometrioid carcinomas (OEC) of low grade have characteristic morphologic features, but high-grade tumors can mimic high-grade serous and undifferentiated carcinomas. We reviewed tumors initially diagnosed as OEC to determine whether a combination of pathologic and immunohistochemical features can improve histologic subclassification. Tumors initially diagnosed as OEC were reviewed using World Health Organization criteria. We also noted the presence of associated confirmatory endometrioid features (CEFs): (i) squamous metaplasia; (ii) endometriosis; (iii) adenofibromatous background; and (iv) borderline endometrioid or mixed Mullerian component. A tissue microarray was constructed from 27 representative tumors with CEF and 14 without CEF, and sections were stained for WT-1, p16, and p53. Of 109 tumors initially diagnosed as OEC, 76 (70%) tumors were classified as OEC. The median patient age was 55 years, and 75% of patients were younger than 60 years. Ninety-two percent presented with disease confined to the pelvis, and 87% of tumors were unilateral. The median tumor size was 11.8 cm. Only 3% of tumors were high grade (grade 3of 3). Eighty percent of cases had at least 1 CEF, and 59% had at least 2 CEFs. Eleven percent overexpressed p16, 0% overexpressed p53, and 3% expressed WT-1. Only 10% of patients died of disease at last follow-up. Thirty-three (33) tumors, or 30% of tumors originally classified as endometrioid, were reclassified as serous carcinoma (OSC). The median patient age was 54.5 years, and 59% of patients were younger than 60 years of age. Only 27% had disease confined to the pelvis at presentation, 52% of tumors were unilateral, and the median tumor size was 8 cm. Associated squamous differentiation, endometrioid adenofibroma, and endometrioid or mixed Mullerian borderline tumor (CEFs) were not present in any case, but 6% of patients had endometriosis. Approximately one half of the reclassified OSC demonstrated SET-pattern morphology

  3. Inhibition of focal adhesion kinase (FAK) activity prevents anchorage-independent ovarian carcinoma cell growth and tumor progression

    PubMed Central

    Ward, Kristy K.; Tancioni, Isabelle; Lawson, Christine; Miller, Nichol L.G.; Jean, Christine; Chen, Xiao Lei; Uryu, Sean; Kim, Josephine; Tarin, David; Stupack, Dwayne G.; Plaxe, Steven C.; Schlaepfer, David D.

    2013-01-01

    Recurrence and spread of ovarian cancer is the 5th leading cause of death for women in the United States. Focal adhesion kinase (FAK) is a cytoplasmic protein-tyrosine kinase located on chromosome 8q24.3 (gene is Ptk2), a site commonly amplified in serous ovarian cancer. Elevated FAK mRNA levels in serous ovarian carcinoma are associated with decreased (logrank P = 0.0007, hazard ratio 1.43) patient overall survival, but how FAK functions in tumor progression remains undefined. We have isolated aggressive ovarian carcinoma cells termed ID8-IP after intraperitoneal (IP) growth of murine ID8 cells in C57Bl6 mice. Upon orthotopic implantation within the periovarian bursa space, ID8-IP cells exhibit greater tumor growth, local and distant metastasis, and elevated numbers of ascites-associated cells compared to parental ID8 cells. ID8-IP cells exhibit enhanced growth under non-adherent conditions with elevated FAK and c-Src tyrosine kinase activation compared to parental ID8 cells. In vitro, the small molecule FAK inhibitor (Pfizer, PF562,271, PF-271) at 0.1 uM selectively prevented anchorage-independent ID8-IP cell growth with the inhibition of FAK tyrosine (Y)397 but not c-Src Y416 phosphorylation. Oral PF-271 administration (30 mg/kg, twice daily) blocked FAK but not c-Src tyrosine phosphorylation in ID8-IP tumors. This was associated with decreased tumor size, prevention of peritoneal metastasis, reduced tumor-associated endothelial cell number, and increased tumor cell-associated apoptosis. FAK knockdown and re-expression assays showed that FAK activity selectively promoted anchorage-independent ID8-IP cell survival. These results support the continued evaluation of FAK inhibitors as a promising clinical treatment for ovarian cancer. PMID:23275034

  4. NOTCH2 expression is decreased in epithelial ovarian cancer and is related to the tumor histological subtype

    PubMed Central

    Galic, Vijaya; Shawber, Carrie J.; Reeves, Claire; Shah, Monjri; Murtomaki, Aino; Wright, Jason; Herzog, Thomas; Tong, Guo Xia; Kitajewski, Jan

    2014-01-01

    Background: Notch family members function as both oncogenes and tumor suppressors. NOTCH2 is down-regulated in colon cancer, and reduced expression is associated with a less differentiated, more aggressive phenotype, and reduced overall survival. NOTCH2 has also been shown to have pro-apoptotic and growth suppressive effects in thyroid carcinoma, and carcinoid tumors. The expression pattern of NOTCH2 in ovarian cancer is unknown. Methods: An immunohistochemical analysis using a polyclonal antibody to the NOTCH2 intracellular domain was performed on a total of 119 ovarian carcinomas, and 7 serous borderline tumors, arranged onto tissue arrays. Normal ovarian and fallopian tube epithelium were used as controls. Specimens were scored as low or high NOTCH2 expression. The score distributions for the subtypes were analyzed with the chi square test. Results: Fifty two of 61 (85.2%) papillary serous, eight of 13 (61.5%) clear cell, and 23 of 30 (76.7%) endometrioid, demonstrated negative or lower NOTCH2 expression than normal fallopian tubal epithelium or ovarian surface epithelium. In contrast, 10 of 15 (66.7%) mucinous carcinomas had a high level of NOTCH2 expression and consistently demonstrated intense polarized staining (P<.001). The apical expression of NOTCH2 protein present in the normal fallopian tube epithelium and many borderline tumors was absent in the high grade carcinomas, most notably in papillary serous. Conclusion: Decreased NOTCH2 expression is associated with the poorly differentiated serous epithelial ovarian carcinoma histology. Further studies are needed to assess the functional role of NOTCH2 in ovarian cancer and its effect on prognosis. PMID:24707357

  5. Ovarian tumor (OTU)-domain containing viral proteases evade ubiquitin- and ISG15-dependent innate immune responses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ubiquitin (Ub) and interferon stimulated gene product 15 (ISG15) reversibly conjugate to proteins via a conserved LRLRGG C-terminal motif, mediating important innate antiviral responses. The ovarian tumor (OTU) domain represents a superfamily of predicted proteases found in eukaryotic, bacterial, a...

  6. HORMONAL CONTROL OF OVARIAN FUNCTION FOLLOWING CHLOROTRIAZINE EXPOSURE: EFFECT ON REPRODUCTIVE FUNCTION AND MAMMARY GLAND TUMOR DEVELOPMENT

    EPA Science Inventory

    Hormonal Control of Ovarian Function Following Chlorotriazine Exposure: Effect on Reproductive Function and Mammary Gland Tumor Development.

    Ralph L. Cooper, Susan C. Laws, Michael G. Narotsky, Jerome M. Goldman, and Tammy E. Stoker

    Abstract
    The studies review...

  7. Platelets are associated with xenograft tumor growth and the clinical malignancy of ovarian cancer through an angiogenesis-dependent mechanism.

    PubMed

    Yuan, Lei; Liu, Xishi

    2015-04-01

    Platelets are known to facilitate tumor metastasis and thrombocytosis has been associated with an adverse prognosis in ovarian cancer. However, the role of platelets in primary tumour growth remains to be elucidated. The present study demonstrated that the expression levels of various markers in platelets, endothelial adherence and angiogenesis, including, platelet glycoprotein IIb (CD41), platelet endothelial cell adhesion molecule 1 (CD31), vascular endothelial growth factor (VEGF), lysyl oxidase, focal adhesion kinase and breast cancer anti‑estrogen resistance 1, were expressed at higher levels in patients with malignant carcinoma, compared with those with borderline cystadenoma and cystadenoma. In addition, the endothelial markers CD31 and VEGF were found to colocalize with the platelet marker CD41 in the malignant samples. Since mice transplanted with human ovarian cancer cells (SKOV3) demonstrated elevated tumor size and decreased survival rate when treated with thrombin or thrombopoietin (TPO), the platelets appeared to promote primary tumor growth. Depleting platelets using antibodies or by pretreating the cancer cells with hirudin significantly attenuated the transplanted tumor growth. The platelets contributed to late, but not early stages of tumor proliferation, as mice treated with platelet‑depleting antibody 1 day prior to and 11 days after tumor transplantation had the same tumor volumes. By contrast, tumor size in the early TPO‑injected group was increased significantly compared with the late TPO‑injected group. These findings suggested that the interplay between platelets and angiogenesis may contribute to ovarian cancer growth. Therefore, platelets and their associated signaling and adhesive molecules may represent potential therapeutic targets for ovarian cancer. PMID:25502723

  8. Temsirolimus and Bevacizumab in Treating Patients With Advanced Endometrial, Ovarian, Liver, Carcinoid, or Islet Cell Cancer

    ClinicalTrials.gov

    2016-07-05

    Adult Hepatocellular Carcinoma; Advanced Adult Hepatocellular Carcinoma; Endometrial Serous Adenocarcinoma; Localized Non-Resectable Adult Liver Carcinoma; Lung Carcinoid Tumor; Malignant Pancreatic Gastrinoma; Malignant Pancreatic Glucagonoma; Malignant Pancreatic Insulinoma; Malignant Pancreatic Somatostatinoma; Metastatic Digestive System Neuroendocrine Tumor G1; Ovarian Carcinosarcoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Surface Papillary Adenocarcinoma; Pancreatic Alpha Cell Adenoma; Pancreatic Beta Cell Adenoma; Pancreatic Delta Cell Adenoma; Pancreatic G-Cell Adenoma; Pancreatic Polypeptide Tumor; Recurrent Adult Liver Carcinoma; Recurrent Digestive System Neuroendocrine Tumor G1; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Pancreatic Neuroendocrine Carcinoma; Recurrent Primary Peritoneal Carcinoma; Recurrent Uterine Corpus Carcinoma; Regional Digestive System Neuroendocrine Tumor G1; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIA Uterine Corpus Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IIIC Uterine Corpus Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer; Uterine Carcinosarcoma

  9. Identifying metastatic breast tumors using textural kinetic features of a contrast based habitat in DCE-MRI

    NASA Astrophysics Data System (ADS)

    Chaudhury, Baishali; Zhou, Mu; Goldgof, Dmitry B.; Hall, Lawrence O.; Gatenby, Robert A.; Gillies, Robert J.; Drukteinis, Jennifer S.

    2015-03-01

    The ability to identify aggressive tumors from indolent tumors using quantitative analysis on dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) would dramatically change the breast cancer treatment paradigm. With this prognostic information, patients with aggressive tumors that have the ability to spread to distant sites outside of the breast could be selected for more aggressive treatment and surveillance regimens. Conversely, patients with tumors that do not have the propensity to metastasize could be treated less aggressively, avoiding some of the morbidity associated with surgery, radiation and chemotherapy. We propose a computer aided detection framework to determine which breast cancers will metastasize to the loco-regional lymph nodes as well as which tumors will eventually go on to develop distant metastses using quantitative image analysis and radiomics. We defined a new contrast based tumor habitat and analyzed textural kinetic features from this habitat for classification purposes. The proposed tumor habitat, which we call combined-habitat, is derived from the intersection of two individual tumor sub-regions: one that exhibits rapid initial contrast uptake and the other that exhibits rapid delayed contrast washout. Hence the combined-habitat represents the tumor sub-region within which the pixels undergo both rapid initial uptake and rapid delayed washout. We analyzed a dataset of twenty-seven representative two dimensional (2D) images from volumetric DCE-MRI of breast tumors, for classification of tumors with no lymph nodes from tumors with positive number of axillary lymph nodes. For this classification an accuracy of 88.9% was achieved. Twenty of the twenty-seven patients were analyzed for classification of distant metastatic tumors from indolent cancers (tumors with no lymph nodes), for which the accuracy was 84.3%.

  10. OVARIAN CANCER

    PubMed Central

    Cho, Kathleen R.; Shih, Ie-Ming

    2009-01-01

    Ovarian carcinomas are a heterogeneous group of neoplasms traditionally sub-classified based on type and degree of differentiation. Although current clinical management of ovarian carcinoma largely fails to take this heterogeneity into account, it is becoming evident that each major histological type has characteristic genetic defects that deregulate specific signaling pathways in the tumor cells. Moreover, within the most common histological types, the molecular pathogenesis of low-grade versus high-grade tumors appears to be largely distinct. Mouse models of ovarian carcinoma have been developed that recapitulate many of the morphological features, biological behavior, and gene expression patterns of selected subtypes of ovarian cancer. Such models will likely prove useful for studying ovarian cancer biology and for pre-clinical testing of molecularly targeted therapeutics, which may ultimately lead to better clinical outcomes for women with ovarian cancer. PMID:18842102

  11. Anti-KDEL-coated nanoparticles: a promising tumor targeting approach for ovarian cancer?

    PubMed

    Delie, Florence; Ribaux, Pascale; Petignat, Patrick; Cohen, Marie

    2012-11-01

    The purpose of this study was to target ovarian cancer cells by coupling paclitaxel (Tx)-loaded nanoparticles (NPs-Tx) to antibodies against KDEL sequence, able to recognize GRP94 and GRP78 that are located at cell surface in cancer cells whereas they are in the endoplasmic reticulum in healthy cells. Tx-loaded poly (DL-lactic acid) nanoparticles coated with anti-KDEL antibodies (NPs-Tx-KDEL) were successfully prepared and characterized. Interaction between tumor cells and NPs-Tx or NPs-Tx-KDEL was observed by microscopy with fluorescently labeled NPs and the efficacy of the different formulations was compared by a viability assay. Particles functionalized with monoclonal antibodies (mAb) showed a higher binding to the cells even though the internalization rate appeared limited. The effect of NPs-Tx-KDEL on cell viability (proliferation) was compared to Tx, NPs, NPs-Tx, anti-KDEL mAb or anti-KDEL mAb in combination with NPs-Tx in Bg-1 ovarian cell line. Our data indicate that NPs-Tx-KDEL significantly increase sensitivity of Bg-1 cells to Tx compared to other treatments. This study confirms the interest of anti-cancer therapy by targeting cell surface GRP78 and GRP94 on cancer cells, and demonstrates the efficiency of coupling KDEL antibodies to NPs. PMID:22713763

  12. Targeted overexpression of luteinizing hormone in transgenic mice leads to infertility, polycystic ovaries, and ovarian tumors.

    PubMed Central

    Risma, K A; Clay, C M; Nett, T M; Wagner, T; Yun, J; Nilson, J H

    1995-01-01

    Hypersecretion of luteinizing hormone (LH) is implicated in infertility and miscarriages in women. A lack of animal models has limited progress in determining the mechanisms of LH toxicity. We have recently generated transgenic mice expressing a chimeric LH beta subunit (LH beta) in gonadotropes. The LH beta chimera contains the C-terminal peptide of the human chorionic gonadotropin beta subunit. Addition of this peptide to bovine LH beta resulted in a hormone with a longer half-life. Furthermore, targeted expression of the LH beta chimera led to elevated LH levels and infertility in female transgenics. These mice ovulated infrequently, maintained a prolonged luteal phase, and developed pathologic ovarian changes such as cyst formation, marked enlargement of ovaries, and granulosa cell tumors. Testosterone and estradiol levels were increased compared to nontransgenic littermates. An unusual extragonadal phenotype was also observed: transgenic females developed hydronephropathy and pyelonephritis. The pathology observed demonstrates a direct association between abnormal secretion of LH and infertility and underscores the utility of the transgenic model for studying how excess LH leads to cyst formation, ovarian tumorigenesis, and infertility. Images Fig. 2 Fig. 3 Fig. 5 PMID:7877975

  13. Analysis of ESR1 mutation in circulating tumor DNA demonstrates evolution during therapy for metastatic breast cancer.

    PubMed

    Schiavon, Gaia; Hrebien, Sarah; Garcia-Murillas, Isaac; Cutts, Rosalind J; Pearson, Alex; Tarazona, Noelia; Fenwick, Kerry; Kozarewa, Iwanka; Lopez-Knowles, Elena; Ribas, Ricardo; Nerurkar, Ashutosh; Osin, Peter; Chandarlapaty, Sarat; Martin, Lesley-Ann; Dowsett, Mitch; Smith, Ian E; Turner, Nicholas C

    2015-11-11

    Acquired ESR1 mutations are a major mechanism of resistance to aromatase inhibitors (AIs). We developed ultra high-sensitivity multiplex digital polymerase chain reaction assays for ESR1 mutations in circulating tumor DNA (ctDNA) and investigated the clinical relevance and origin of ESR1 mutations in 171 women with advanced breast cancer. ESR1 mutation status in ctDNA showed high concordance with contemporaneous tumor biopsies and was accurately assessed in samples shipped at room temperature in preservative tubes. ESR1 mutations were found exclusively in estrogen receptor-positive breast cancer patients previously exposed to AI. Patients with ESR1 mutations had a substantially shorter progression-free survival on subsequent AI-based therapy [hazard ratio, 3.1; 95% confidence interval (CI), 1.9 to 23.1; P = 0.0041]. ESR1 mutation prevalence differed markedly between patients who were first exposed to AI during the adjuvant and metastatic settings [5.8% (3 of 52) versus 36.4% (16 of 44), respectively; P = 0.0002]. In an independent cohort, ESR1 mutations were identified in 0% (0 of 32; 95% CI, 0 to 10.9) tumor biopsies taken after progression on adjuvant AI. In a patient with serial sampling, ESR1 mutation was selected during metastatic AI therapy to become the dominant clone in the cancer. ESR1 mutations can be robustly identified with ctDNA analysis and predict for resistance to subsequent AI therapy. ESR1 mutations are rarely acquired during adjuvant AI but are commonly selected by therapy for metastatic disease, providing evidence that mechanisms of resistance to targeted therapy may be substantially different between the treatment of micrometastatic and overt metastatic cancer. PMID:26560360

  14. Metastatic tumors in the jaw bones: A retrospective clinicopathological study of 12 cases at Tertiary Cancer Center

    PubMed Central

    Nawale, Kundan Kisanrao; Vyas, Monika; Kane, Shubhada; Patil, Asawari

    2016-01-01

    Introduction: The metastatic disease of the jaw bones is very uncommon and accounts for approximately 1% of all malignancies of jaw. The most common location is molar region of mandible. Metastasis may go undetected on a routine skeletal survey for assessment of metastasis and rarely includes jaw bones. Aims and Objective: The aim of the study is to analyze primary malignancies in metastatic jaw tumors. Materials and Methods: We retrospectively studied clinicopathological features of 12 patients of metastasis to jaw bones diagnosed at tertiary cancer center between 2003 and 2011. All H and E and immunohistochemical slides were reviewed by two pathologists and relevant details were noted. Results: There were eight female and four male patients, with age range 12–71 years with metastases to jaws. All of them involved mandible with one case also showing the involvement of frontal sinuses. The types of metastatic tumors include adenocarcinoma (six cases), papillary thyroid carcinoma (four cases), carcinoma with neuroendocrine differentiation (one case) and neuroblastoma (one case). The diagnosis was made on biopsies in eight cases and on hemimandibulectomy in four cases. The primary site was known at the time of presentation only in four cases, all of them being thyroid carcinomas. Primary site was determined in seven cases after immunohistochemical workup on metastatic tumor and further investigations, whereas the primary site of carcinoma with neuroendocrine differentiation was unknown. Conclusion: Metastasis to jaw bones is rare and may be the first manifestation of unknown primary. A lesion predominantly involving bone with unusual morphology should raise a possibility of metastasis. PMID:27601818

  15. Everolimus and Letrozole in Treating Patients With Recurrent Hormone Receptor Positive Ovarian, Fallopian Tube, or Primary Peritoneal Cavity Cancer

    ClinicalTrials.gov

    2016-06-14

    Ovarian Endometrioid Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Serous Surface Papillary Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Ovarian Germ Cell Tumor; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Ovarian Carcinoma

  16. Changes in Brain Function in Patients With Stage I, Stage II, Stage III, or Stage IV Ovarian, Primary Peritoneal, or Fallopian Tube Cancer Who Are Receiving Chemotherapy

    ClinicalTrials.gov

    2016-02-09

    Cognitive Side Effects of Cancer Therapy; Malignant Ovarian Epithelial Tumor; Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Carcinosarcoma; Ovarian Choriocarcinoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Dysgerminoma; Ovarian Embryonal Carcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Germ Cell Tumor; Ovarian Mucinous Cystadenocarcinoma; Ovarian Polyembryoma; Ovarian Sarcoma; Ovarian Serous Cystadenocarcinoma; Ovarian Teratoma; Ovarian Yolk Sac Tumor; Stage I Ovarian Cancer; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IA Ovarian Germ Cell Tumor; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Cancer; Stage IB Ovarian Germ Cell Tumor; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Cancer; Stage IC Ovarian Germ Cell Tumor; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Primary Peritoneal Cancer; Undifferentiated Ovarian Carcinoma

  17. Stereotactic Body Radiation Therapy for Primary, Recurrent, and Metastatic Tumors in the Head-and-Neck Region

    SciTech Connect

    Siddiqui, Farzan; Patel, Mehul; Khan, Mumtaz; McLean, Scott; Dragovic, Jadranka; Jin, J.-Y.; Movsas, Benjamin; Ryu, Samuel

    2009-07-15

    Purpose: To determine the feasibility, safety, and efficacy of stereotactic body radiation therapy (SBRT), also known as radiosurgery, in patients with head-and-neck cancers. Methods and Materials: Patients with pathologically proven malignant lesions in the head-and-neck region were treated using single-dose SBRT (S-SBRT) or fractionated SBRT (F-SBRT). Radiation doses were either single-fraction 13-18 Gy for S-SBRT or 36-48 Gy in five to eight fractions for F-SBRT. Response evaluation was based on clinical examinations and computed tomography/magnetic resonance imaging scans. Pre- and post-SBRT tumor dimensions were measured in three axes, and tumor volumes were calculated. Response evaluation also was performed using World Health Organization criteria. Results: Fifty-five lesions were treated in 44 patients (25 men, 19 women). There were three groups of patients: those with primary (n = 10), recurrent (n = 21), and metastatic tumors (n = 13). The predominant histologic type was squamous cell carcinoma (n = 33). The majority of lesions were treated using F-SBRT (n = 37). Based on radiographic and clinical assessment, a 77% (complete + partial response) response rate was noted. Percentage of reduction in tumor volume was 52% {+-} 38% based on follow-up scans in 24 patients. Tumor control rates at 1 year were 83.3% and 60.6% in the primary and recurrent groups, respectively. Median overall survival was 28.7, 6.7, and 5.6 months for the primary, recurrent, and metastatic groups, respectively. Radiation Therapy Oncology Group Grade 1-2 mucositis was noted in all patients treated for oropharyngeal or laryngeal lesions. Conclusions: The SBRT in single or fractionated doses offers a viable treatment option for selected patients with primary, recurrent, and metastatic head-and-neck cancers with functional preservation.

  18. Comparative Analysis of Efficacy and Safety of Multisession Radiosurgery to Single Dose Radiosurgery for Metastatic Brain Tumors

    PubMed Central

    Lee, Gwang Soo; Kim, Ji Hoon; Park, Hyung Ki; Park, Suk Que; Kim, Ra Sun; Jang, Jae Chil

    2015-01-01

    Background The purpose of this study is to compare the efficacy and safety of multisession radiosurgery to those of single dose radiosurgery for metastatic brain tumors. Methods Between February 2008 and February 2012, 90 patients with 196 metastatic brain tumors were treated with cyberknife radiosurgery, and we reviewed these patients retrospectively. Among them, 57 patients underwent single dose radiosurgery, and 33 patients multisession radiosurgery. Tumors involving the eloquent area and large tumors (>5 cc) were treated with multisession radiosurgery. The median tumor volume and the median treatment dose of single dose radiosurgery were 2.05±0.72 cc and 19.76±1.54 Gy respectively, and in the case of multisession radiosurgery, 5.30±1.70 cc and 29.6±1.70 Gy respectively. The frequency of multisession dose was 3 to 5 times, on average 3.55 times, and 8.91 Gy were given per 1 session on average. Results The overall survival (OS) of multisession radiosurgery was 16.0 months, whereas that of single dose radiosurgery was 11.5 months. The radiologic tumor response rates were 90% in single dose radiosurgery and 95.4% in multisession radiosurgery, respectively. Over 6-month and 1-year periods, the OS rates of single dose radiosurgery were 71.4% and 44.9%, whereas those of multisession radiosurgery were 69.1% and 58.3%, respectively (p=0.83). Toxicities were seen in 18.1% in the single dose radiosurgery group versus 4% in the multisession radiosurgery group. The difference was significant (p<0.05). Conclusion In this study, the multisession radiosurgery group, despite the location and size constraints, did not differ from the single dose radiosurgery group when comparing the survival and recurrence rates, but complications and toxicity were lower. Thus, multisession radiosurgery is thought to be beneficial for treatment of large tumors and tumors located in the eloquent area. PMID:26605264

  19. Toward an integrative analysis of the tumor microenvironment in ovarian epithelial carcinoma.

    PubMed

    Serio, Ryan N

    2012-08-01

    Ovarian epithelial carcinomas are heterogeneous malignancies exhibiting great diversity in histological phenotypes as well as genetic and epigenetic aberrations. A general early event in tumorigenesis is regional dissemination into the peritoneal cavity. Initial spread to the peritoneum is made possible by cooperative signaling between a wide array of molecules constituting the tissue microenvironment in the coelomic epithelium. Changes in the activity of key microenvironmental components not constitutively expressed in normal tissue, including several disclosed adhesion molecules, growth factors, proteases, and G-protein coupled receptors (GPCRs), coordinate the transition. Remodeling of the extracellular matrix (ECM) and subsequent cell surface interactions enable transformation by promoting chromosomal instability (CIN) and stimulating several common signal transduction cascades to prepare the tissue for harboring and facilitating growth, angiogenesis and metastasis of the developing tumor. PMID:22109660

  20. The pro-inflammatory peptide LL-37 promotes ovarian tumor progression through recruitment of multipotent mesenchymal stromal cells.

    PubMed

    Coffelt, Seth B; Marini, Frank C; Watson, Keri; Zwezdaryk, Kevin J; Dembinski, Jennifer L; LaMarca, Heather L; Tomchuck, Suzanne L; Honer zu Bentrup, Kerstin; Danka, Elizabeth S; Henkle, Sarah L; Scandurro, Aline B

    2009-03-10

    Bone marrow-derived mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs) have been shown to engraft into the stroma of several tumor types, where they contribute to tumor progression and metastasis. However, the chemotactic signals mediating MSC migration to tumors remain poorly understood. Previous studies have shown that LL-37 (leucine, leucine-37), the C-terminal peptide of human cationic antimicrobial protein 18, stimulates the migration of various cell types and is overexpressed in ovarian, breast, and lung cancers. Although there is evidence to support a pro-tumorigenic role for LL-37, the function of the peptide in tumors remains unclear. Here, we demonstrate that neutralization of LL-37 in vivo significantly reduces the engraftment of MSCs into ovarian tumor xenografts, resulting in inhibition of tumor growth as well as disruption of the fibrovascular network. Migration and invasion experiments conducted in vitro indicated that the LL-37-mediated migration of MSCs to tumors likely occurs through formyl peptide receptor like-1. To assess the response of MSCs to the LL-37-rich tumor microenvironment, conditioned medium from LL-37-treated MSCs was assessed and found to contain increased levels of several cytokines and pro-angiogenic factors compared with controls, including IL-1 receptor antagonist, IL-6, IL-10, CCL5, VEGF, and matrix metalloproteinase-2. Similarly, Matrigel mixed with LL-37, MSCs, or the combination of the two resulted in a significant number of vascular channels in nude mice. These data indicate that LL-37 facilitates ovarian