John Durfee

A heat shock protein 70-based vaccine with enhanced immunogenicity for clinical use

In previous studies, we have shown that heat shock protein 70-peptide complexes (HSP70.PCs) derived from the fusion of dendritic cells (DCs) to tumor cells (HSP70.PC-F) possess superior properties compared with HSP70.PCs from tumor cells. HSP70.PC-F are more effective in stimulation of DC maturation and induction of CTL that are able to provide protection of mice against challenge with tumor cells. To develop an improved formulation of HSP70.PC-based tumor vaccine for patient use, we extracted HSP70.PC-F from DCs fused to patient-derived ovarian cancer cells or established human breast cancer cells and examined their properties as tumor vaccines. HSP70.PC-F induced T cells that expressed higher levels of IFN-γ and exhibited increased levels of killing of tumor cells, compared with those induced by HSP70.PC derived from tumor cells. Enhanced immunogenicity of HSP70.PC-F was associated with improved composition of the vaccine, including increased content of tumor Ags and their processed intermediates, and the detection of other heat shock proteins (HSPs) such as HSP90 and HSP110. The present study has therefore provided an alternative approach to preparation of HSP-based vaccines using DC/tumor fusion technology and gentle and rapid isolation of HSP peptide complexes.

Induction of cytotoxic T lymphocytes against ovarian cancer-initiating cells.

The majority of patients with stage III/IV ovarian carcinoma that respond initially to standard therapies ultimately undergo relapse due to the survival of small populations of cells with tumor‐initiating potential. These ovarian cancer (OVCA)‐initiating cells (OCIC) are sometimes called cancer stem cells (CSC) because they express stem cell markers, and can survive conventional therapies such as chemotherapy, which usually target rapidly replicating tumor cells, and give rise to recurrent tumors that are more chemo‐resistant and more aggressive. Thus, it would be desirable to develop a therapy that could selectively target OCIC and be used to complement the conventional therapies. In this study, we isolated a subset of OVCA cells with a CD44+ phenotype in samples from patients with OVCA that possess CSC properties including the formation of spheroids in culture, self‐renewal and the ability to be engrafted in immune‐compromised mice. We next explored the use of immunotherapy using fusions of dendritic cells and OCIC to specifically target the OCIC subpopulations. Fusion cells (FCs) prepared in this way activated T cells to express elevated levels of IFN‐γ with enhanced killing of CD44+ OVCA cells. We envision a combined approach where conventional therapies such as chemotherapy kill the bulk of tumor cells, whereas OCIC‐reactive cytotoxic T lymphocytes target the resistant OCIC fraction. A combined therapy such as this may represent a promising approach for the treatment of OVCA.

Adenocarcinoma of the Endometrium: An Institutional Review.

BACKGROUND: Many oncologists regard endometrial cancer as a relatively benign and easily treatable gynecologic tumor. Inadequate care can result in poor outcomes. METHODS: The authors review the epidemiology and pathology of the disease, and they compare disease characteristics and outcomes of FIGO staging with their own 11-year experience at a tertiary referral center. RESULTS: Patients referred to tertiary referral centers tend to present with more advanced stages of disease than those reported by FIGO, although the profile of histologic types is similar. CONCLUSIONS: Prevention and early detection of endometrial cancer can minimize the impact of this disease. Complete staging and tumor removal including extrafascial hysterectomy with bilateral salpingo-oophorectomy, pelvic lymphadenectomy, and selective paraaortic lymphadenectomy are the cornerstones of surgical therapy.

Bilateral ureteral obstruction secondary to ovarian remnants with endometriosis.

A 45-year-old white nulligravida had abdominal hysterectomy and bilateral salpingo-oophorectomy in 1980 for severe endometriosis and was taking unopposed estrogen replacement therapy (ERT) since September 1999. She developed bilateral colicky lower quadrant pain and intravenous pyelogram (IVP) found bilateral ureteral strictures that were treated with retrograde stent placement. Computed tomography (CT) showed bilateral hypogastric adenopathy (nodular masses up to 3 cm in diameter), with ureteral obstruction. Computed tomography-guided biopsy of the right hypogastric area showed endometriosis. At laparotomy, bilateral 3 3 6-cm nodular pelvic masses were found contiguous with the ovarian vessels. They encased the pelvic portion of the ureters and appeared to be ovarian remnants with endometriosis. During attempted ureterolysis, intrinsic ureteral endometriosis and severe fibrosis were seen, and no peristalsis was noted in those segments. The mass on each side was resected, including the involved ureteral segments (6 cm on the left and 5 cm on the right), leaving 2 cm of bilateral distal ureter. Bilateral ureteroneocystostomies were done, and the pathology report confirmed bilateral ovarian remnants that contained extensive endometriosis with involvement of both ureters and extensive ureteral fibrosis. The ureteral stents were removed 6 weeks postoperatively, and IVP showed normal drainage. The woman complained of hot flushes and was prescribed combined estrogen and progestin.

Hormonal Therapy for Menopausal Symptoms in Gynecologic Cancer Survivors

The cases detailed above highlight symptom burden faced by patients rendered surgically menopausal in the setting of gynecological cancer and management considerations that treating healthcare providers must consider when helping to optimize the quality of life for this population. Potential options for therapy, special considerations, side effects, and treatment regimens for vasomotor symptom management in gynecological cancer survivors will be discussed.

Cancer and the world's poor: What's a gynecologic cancer specialist to do?

Women in low- and middle-income countries (LMICs) face a drastically increased burden of cervical cancer and the same burden of other gynecologic cancers as do women in high-income countries, yet there are few resources or specialists to meet their needs. 85% of deaths from cervical cancer occur in LMICs. As the population of these regions age, and as death from infectious diseases decrease, this burden will increase further without strong intervention. There are few cancer specialists in LMICs and training in gynecologic cancer care is rare. Gynecologic cancer specialists are uniquely positioned to meet this challenge as advocates, educators and experts. On behalf of the SGO International Committee, we call on our colleagues to meet this historic challenge.