Prognostic role of immunosuppressive acidic protein in advanced ovarian cancer

OBJECTIVE: Our purpose was to investigate immunosuppressive acidic protein in the prognostic characterization of advanced ovarian cancer. STUDY DESIGN: Serum levels of immunosuppressive protein were prospectively measured in 80 patients with untreated ovarian carcinoma. To evaluate the prognostic significance of immunosuppressive acidic protein levels, cutoff points were studied every 50 μg/ml between 450 and 1350 μg/ml. RESULTS: Pretreatment immunosuppressive acidic protein levels were not significantly associated with stage, histotype, grade of differentiation, postoperative residual tumor, and response to chemotherapy. The most significant association with survival was observed at a cutoff value of 1100 μg/ml (p = 0.0089). In the univariate analysis for overall survival, International Federation of Gynecology and Obstetrics stage and immunosuppressive acidic protein status were found to have a role in predicting ovarian cancer prognosis. In the multivariate analysis only immunosuppressive acidic protein status was significantly associated with survival. A statistical correlation was found between serum levels and overall survival (p = 0.0104, χ² 6.56), including immunosuppressive acidic protein as a continuous variable. CONCLUSION: Our data suggest that immunosuppressive acidic protein assay is a potentially useful tool in the prognostic characterization of advanced ovarian cancer. (Am J Obstet Gynecol 1996;175:1606-10.)     

A small molecule Smac mimic potentiates TRAIL-mediated cell death of ovarian cancer cells

OBJECTIVES: Ovarian cancer remains a leading cause of death in women and development of new therapies is essential. Second mitochondria derived activator of caspase (Smac) has been described to sensitize for apoptosis. We have explored the proapoptotic activity of a small molecule mimic of Smac/DIABLO on ovarian cancer cell lines (A2780 cells and its chemoresistant derivatives A2780/ADR and A2780/DDP), cancer cell lines and in primary ovarian cancer cells. METHODS: The effects of a small molecule mimic of Smac/DIABLO on ovarian cancer cell lines and primary ovarian cancer cells were determined by cell proliferation, apoptosis and biochemical assays. RESULTS: This compound added alone elicited only a weak proapoptotic effect; however, it strongly synergizes with tumor necrosis factor-related apoptosis inducing ligand (TRAIL) or agonistic TRAILR2 antibody (Lexatumumab) in inducing apoptosis of ovarian cancer cells. CONCLUSIONS: These observations suggest that small molecule mimic of Smac/DIABLO could be useful for the development of experimental strategies aiming to treat ovarian cancer. Interestingly, in addition to its well known proapoptotic effects, Smac/DIABLO elicited a significant increase of pro-caspase-3 levels.     

Analysis of 138 consecutive ovarian cancer patients: Incidence and characteristics of familial cases

Eight families with two or more first-degree relatives affected with ovarian carcinoma were identified among a series of 138 consecutive ovarian cancer patients. History of breast cancer was reported in six of the eight families. Five of 19 patients with familial cancer developed ovarian cancer as a second primary tumor following breast carcinoma, whereas only 6/130 sporadic cases had a previous history of breast cancer. No significant difference was detected in clinical and pathological features between sporadic and familial cases. However, in three high-risk families ovarian cancer tended to develop at a younger age compared with other familial cases and with sporadic occurrences, and nulliparity was less frequent in the familial group. These observations emphasize the need to take into account multiple factors-in addition to positive family history-for the evaluation of genetic predisposition to ovarian carcinoma.     

Mutations of the D310 mitochondrial mononucleotide repeat in primary tumors and cytological specimens

A mononucleotide repeat (D310) in mitochondrial DNA has been recently identified as a mutational hot spot in primary tumors. We analyzed 56 tumors for insertion/deletion mutations in the D310 repeat. A total of 13 mutations were detected. The highest frequency of mutations was found for cervical cancer, followed by bladder tumors, breast cancer and endometrial neoplasia. No alterations were observed in four patients suspected of malignancy but without evidence of malignant tumor. We detected identical changes in four of four urine sediments from patients with bladder cancer and in three of three fine needle aspirates of patients with breast cancer. Our results indicate that D310 abnormalities are detectable in cytology specimens from patients with cancer and support the notion that D310 analysis may represent a new molecular tool for cancer detection.     

Epidermal growth factor levels in human breast cyst fluid

Epidermal growth factor (EGF) seems to modulate the in vitro and in vivo growth of normal and neoplastic breast cells. We determined, by a radio-receptor assay, EGF levels in cyst fluid and in plasma of patients with gross cystic disease of the breast. The mean levels of EGF were lower in plasma than in breast cyst fluid (BCF) (p less than 0.001). In BCF of apocrine cysts we found higher EGF levels than in flattened cysts (p less than 0.001). The EGF content of apocrine BCF seems to be under sex steroid hormone control, being higher in reproductive age than in post menopause (p less than 0.05). Since it has been reported that patients with apocrine cysts are at a greater risk of developing breast cancer, we hypothesize that the high EGF concentration in apocrine BCF may play a role in the autocrine breast cyst epithelium growth control and neoplastic transformation.     

Patients treated with neoadjuvant chemotherapy + radical surgery + adjuvant chemotherapy in locally advanced cervical cancer: long-term outcomes,survival and prognostic factors in a single-center 10-year follow-up

We report the long-term follow-up in patients with locally advanced cervical cancer treated with neoadjuvant chemotherapy (NACT) + radical surgery (RS) + adjuvant chemotherapy (ACT) analyzing prognostic factors which may more influence, in a long time, the survival outcome using univariate and multivariate analysis. In this study, we included all patients with diagnosis of locally advanced cervical cancer (IB2-IIB) treated with NACT + RS + ACT from June 2000 and February 2007 as previously described by Angioli et al. (Gynecol Oncol 127(2):290–6, 2012). The primary end-point of the study was overall survival (OS) in patients with node metastases and in those without positive lymph nodes at the end of 10-year follow-up in order to confirm the prognostic role of nodes involvement for a long period. Moreover, we analyzed the impact of other prognostic factors, such as histotype, tumor size, grading and parametrial invasion. Secondary end-point was evaluated in the subgroup of patients with positive nodes the following prognostic factors: number of positive lymph nodes and site of positive lymph nodes. In the subgroup of patients with positive nodes, the OS was 63 %, and in that with negative nodes, the OS was 75 %. On multivariate analysis, the number of nodal metastases, parametrial involvement, grading and the lesion diameter were noted to be significant factors in determining OS. Neither the histotype nor the lymph nodal site is related to survival. Results suggest that CT alone may be an alternative postoperative therapy for patients with cervical cancer.