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Biomedical subjects

Stephen C Rubin

Publications and source records attributed to Stephen C Rubin.

27 records · Page 2Linked to original sources
PubMed2003

Vaginal cuff recurrence of endometrial cancer treated by laparoscopic-assisted vaginal hysterectomy.

BACKGROUND: Laparoscopic-assisted vaginal hysterectomy (LAVH) has been suggested as an alternative to total abdominal hysterectomy (TAH) for the treatment of early endometrial cancer. Although studies have reported good results with equivalent rates of recurrence and survival, the need for use of intrauterine manipulators during the LAVH raises the concern for operative dissemination of tumor cells. CASES: We report three patients with stage I, noninvasive or superficially invasive endometrial cancer with vaginal cuff recurrence within 9 months of treatment by LAVH. CONCLUSION: While LAVH may be a technically acceptable alternative to TAH for the management of early-stage endometrial cancer, its routine use should be undertaken with caution, as the long-term risks for recurrence and survival have yet to be defined in a randomized, controlled fashion.

Aged↗
PubMed2003

Expression of endocrine gland-derived vascular endothelial growth factor in ovarian carcinoma.

The first tissue-specific angiogenic molecule, endocrine gland-derived vascular endothelial growth factor (EG-VEGF), was identified recently in human ovary, raising hopes of developing tumor type-specific angiogenesis inhibitors. In the present study, we analyzed the expression of EG-VEGF mRNA in normal human tissues and ovarian neoplasms by quantitative real-time reverse transcription-PCR. EG-VEGF mRNA was expressed in all ovarian neoplasms examined. No significant difference was identified among benign, low malignant potential neoplasms or stage I ovarian cancer, all of which exhibited 2-fold lower mRNA levels compared with normal premenopausal ovaries. EG-VEGF mRNA levels further decreased in late stage compared with early stage carcinomas (P < 0.05) and were consistently lower in laser capture microdissected tumor islets compared with surrounding stroma. EG-VEGF was undetectable by reverse transcription-PCR in 17 established epithelial ovarian cancer cell lines or in cultured human ovarian surface epithelial cells, whereas it was detected in peripheral blood as well as tumor-infiltrating T lymphocytes. Finally, in contrast to VEGF, EG-VEGF mRNA levels did not correlate with clinical outcome in advanced ovarian carcinoma. These results suggest that EG-VEGF is most likely derived from nonepithelial components of ovarian carcinomas and may play a marginal role in promoting angiogenesis in advanced ovarian carcinoma. We postulate that EG-VEGF-targeted antiangiogenic therapy may prove useful in early stage but not in advanced stage ovarian carcinoma.

Angiogenesis Inducing Agents↗
PubMed2003

TRANCE- and CD40 ligand-matured dendritic cells reveal MHC class I-restricted T cells specific for autologous tumor in late-stage ovarian cancer patients.

PURPOSE: The use of mature dendritic cells (DCs) presenting tumor-associated antigens (TAAs) to trigger tumor-specific T cells in vivo or in vitro represents a promising approach for cancer immunotherapy. We hypothesized that tumor antigens, mostly unidentified, are present on ovarian tumor cells and that mature DCs could be used to generate tumor-specific responses in unprimed patients. We also sought to measure preexisting antitumor immunity in patients with advanced ovarian cancer. EXPERIMENTAL DESIGN: Autologous DCs from 10 patients with ovarian cancer were pulsed with killed autologous primary tumors as a source of TAAs. DCs were then cultured in the presence of tumor necrosis factor alpha + TRANCE (tumor necrosis factor-related activation-induced cytokine) to induce maturation. Mature TAA-pulsed DCs were used in vitro to stimulate tumor-specific peripheral blood T cells. RESULTS: TRANCE and CD40 ligand were effective at maturing DCs. T-cell lines were generated in vitro that were capable of secreting IFN-gamma in response to autologous tumor. These tumor-specific T cells were MHC class I restricted. The frequency of tumor-specific T cells in uncultured cells from malignant ascites fluid and peripheral blood was measured in the same patients. CONCLUSIONS: IFN-gamma-secreting tumor-specific T cells were demonstrated at baseline in uncultured T cells from some unvaccinated ovarian cancer patients; however, the T cells could not kill autologous tumor. These data demonstrate that mature DCs presenting tumor antigens from engulfed autologous tumors can be used to augment antitumor immunity in vitro in patients with epithelial ovarian cancer. The results support the feasibility of therapeutic vaccination of ovarian cancer patients.

Adult↗
PubMed2002

Replication-selective herpes simplex virus type 1 mutant therapy of cervical cancer is enhanced by low-dose radiation.

Herpes simplex virus type 1 (HSV-1)-based oncolytic treatment is a promising therapeutic approach for malignancy. Recombinant strains of HSV-1 containing mutations in the ICP 34.5 protein have been shown to replicate preferentially in rapidly proliferating malignant cells, resulting in a direct cytolytic effect. We assessed the efficacy of multimutated HSV-1 strains on human cervical cancer, and then used these viruses in combination with radiation therapy, the standard treatment for cervical cancer. The HSV-1 mutants 4009, 7020, 3616, and G207 induced significant lysis of three established human cervical cancer cell lines in vitro in a dose-dependent manner. G207 intratumoral treatment of established subcutaneous C33a tumors in severe combined immunodeficient (SCID) mice significantly reduced tumor burden by 50%. Weekly and triweekly treatments improved efficacy and inhibited flank tumor growth in an administration frequency-dependent manner without toxicity. Combination therapy of a low dose of radiation (1.5 or 3 Gy) and replication-selective HSV mutants infection exhibited increased antitumor effects against cervical cancer cells in vitro. The in vivo effect of G207 combined with low-dose radiation was studied in Me180 xenografts in athymic mice. Treatment of established Me180 tumor nodules with 3 Gy followed by intratumoral G207 administration greatly improved efficacy, resulting in 42% complete eradication of tumor. In conclusion, single and multiple intratumoral injections of G207 significantly reduced tumor burden in xenogeneic models of cervical cancer, and the addition of low-dose radiation further potentiated the effect. These results suggest that replication-selective HSV-1 mutants may be potent oncolytic agents for the treatment of cervical cancer.

Animals↗
PubMed2002

Tumor-associated macrophages as a source of functional dendritic cells in ovarian cancer patients.

We have generated dendritic cells (DCs) from tumor-associated macrophages (TAMs) obtained from ascites fluid or tumor specimens of ovarian cancer patients, and compared them phenotypically and functionally to DCs derived from the patients' peripheral blood mononuclear cells (PBMCs). Both immature and mature DCs could be generated from TAMs. However, TAM-derived DCs underwent maturation to a lesser degree than PBMC-derived DCs, as measured by DC receptor surface expression. Nonetheless, in allogeneic mixed lymphocyte reactions, TAM-derived DCs stimulated T cell proliferation as efficiently as PBMC-derived DCs. In addition, TAM-derived DCs presenting tumor Ags were capable of stimulating IFN-gamma secretion by tumor-specific T cell lines. Thus, TAMs isolated from ovarian cancer patients can be used to generate significant numbers of DCs. Therefore, TAMs have potential use for either ex vivo or in vivo DC-based immunotherapy, particularly in individuals in which more conventional sources of DCs have been depleted.

Adenocarcinoma↗
PubMed2002

The clinical course of deep vein thrombosis in patients with gynecologic cancer.

OBJECTIVE: The aim of this study was to evaluate the survival of gynecologic cancer patients diagnosed with deep vein thrombosis. METHODS: We retrospectively reviewed the charts of patients admitted to our institution with gynecologic malignancy who were diagnosed with deep vein thrombosis (DVT) between 1984 and 1995. Data were collected regarding site, stage, histology, treatment, and proximity of DVT to treatment with surgery, chemotherapy, and radiotherapy. This study was limited to cases of ovarian, uterine, and cervical cancer. Descriptive statistics were generated and the survival of patients from the time of DVT was calculated using the Kaplan and Meier method. Cases were then matched by site, stage, histology, and age to controls without DVT to evaluate the effect of DVT on survival. A Cox regression model was used to assess the effect of multiple variables on survival. RESULTS: A total of 74 cases were identified. Ovarian, uterine, and cervical cancer accounted for 45, 27, and 28% of cases, respectively. Approximately 64% of patients had stage III or greater disease. The median survival of all patients from the time of DVT diagnosis was 7.8 months, with only about 20% of patients surviving at 5 years. Patients with cervical cancer or patients who had radiation therapy within 3 months of DVT diagnosis had significantly lessened survival (P < 0.01) than other patients with DVT. The survival of patients from the time of cancer diagnosis with venous thrombosis was significantly worse than a matched control group without DVT (P < 0.001). On multivariate analysis, there was a twofold greater risk of dying in those patients with gynecologic cancer and DVT. CONCLUSION: The development of DVT in conjunction with a gynecologic malignancy connotes a poor prognosis, especially in patients with cervical cancer. It is possible that this poor prognosis is related to the pathophysiology that results in venous thrombosis and not just the presence of cancer.

Age Factors↗
PubMed2002

Generation of a syngeneic mouse model to study the effects of vascular endothelial growth factor in ovarian carcinoma.

Vascular endothelial growth factor (VEGF) performs multifaceted functions in the tumor microenvironment promoting angiogenesis, suppressing anti-tumor immune response, and possibly exerting autocrine functions on tumor cells. However, appropriate syngeneic animal models for in vivo studies are lacking. Using retroviral transfection and fluorescence-activated cell sorting, we generated a C57BL6 murine ovarian carcinoma cell line that stably overexpresses the murine VEGF164 isoform and the enhanced green fluorescent protein. VEGF164 overexpression dramatically accelerated tumor growth and ascites formation, significantly enhanced tumor angiogenesis, and substantially promoted the survival of tumor cells in vivo. In vitro, VEGF164 overexpression significantly enhanced cell survival after growth factor withdrawal and conferred resistance to apoptosis induced by cis-platin through an autocrine mechanism. VEGF/green fluorescent protein-expressing tumors were not recognized by the adaptive immune system. After vaccination, a specific anti-tumor T-cell response was detected, but tumor growth was not inhibited. This engineered murine carcinoma model should prove useful in the investigation of the role of VEGF in modulating the tumor microenvironment and affecting the complex interactions among angiogenesis mechanisms, anti-tumor immune mechanisms, and tumor cell behavior at the natural state or during therapy in ovarian carcinoma.

Animals↗
PubMed2002

Prophylactic oophorectomy.

Because of the lack of effective alternatives and the simplicity of the procedure, prophylactic oophorectomy is viewed as the best available tool for reducing the individual risk of ovarian cancer. The genetics of hereditary ovarian cancer are described in this chapter and a careful risk-versus-benefit assessment is provided with respect to two populations of patients that appear suitable candidates for this procedure. These include patients with increased risk of developing ovarian cancer due to hereditary genetic predisposition, in which the lifetime risk of ovarian cancer may be as high as 16-65%, depending on the penetrance of the germ-line mutation. Additionally, routine salpingo-oophorectomy in patients over 40 years undergoing scheduled gynaecological surgery or colorectal surgery might reduce the overall incidence of ovarian cancer by as much as 5% in the general population.

Female↗