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John J Kavanagh

Publications and source records attributed to John J Kavanagh.

At least 19 recordsLinked to original sources
PubMed2006

Cyclin E expression is correlated with tumor progression and predicts a poor prognosis in patients with ovarian carcinoma.

BACKGROUND: Cyclins, cyclin dependent kinases (cdks), and their inhibitors act in combination to regulate progression through the cell cycle and often are dysregulated in carcinoma. The authors hypothesized that cyclin E plays an important role in ovarian carcinogenesis and that its overexpression may be an indicator of a poor prognosis. METHODS: Immunohistochemical analysis of cyclin E expression was performed by image analysis in normal ovaries, cystadenomas, tumors of low malignant potential, and 405 primary ovarian carcinomas by using tissue microarray technology. RESULTS: Overexpression of cyclin E was found in 63.2% of the samples and was associated with clear cell, poorly differentiated, and serous carcinoma (P < or = .001), high-grade tumors (P < or = .001), late-stage disease (P = .002), age older than 60 years at the time of diagnosis (P = .04), and suboptimal cytoreduction (P = .001). A high percentage of cyclin E-expressing cells was associated with a poor outcome in univariate and in multivariate analyses. In addition, cyclin E levels also reduced survival in the late-stage disease group and in patients who underwent suboptimal debulking. CONCLUSIONS: Cyclin E was identified as an independent prognostic factor in patients with ovarian carcinoma. The accumulation of cyclin E protein may be a late event in tumorigenesis and may contribute to disease progression in these patients.

Adult↗
PubMed2006

Targeting Aurora kinases in ovarian cancer.

Although recurrent epithelial ovarian cancer initially responds well to current first-line adjuvant therapy, eventually the disease becomes resistant to chemotherapy. Novel strategies are needed to reverse chemoresistance in order to treat relapsed ovarian cancer effectively. One strategy is to target aberrant expression activation of Aurora kinases that are essential for the regulation of chromosome segregation and cytokinesis during mitosis and which play a role in tumourigenesis and progression in a wide range of human tumours, including ovarian cancer. The purpose of this article is to review Aurora kinases and their inhibitors in human epithelial ovarian cancer as an impetus to the development of effective and less toxic regimens for ovarian cancer. In addition, this review tries to define the differences between cytotoxic chemotherapeutic agents and molecular therapeutic agents: both groups of agents have either a single specific target or multiple specific targets, while their differences lie in their toxicity profiles and the way to determine their dosages for further studies. The authors propose that Aurora kinase inhibitors be developed as molecular therapeutic agents in order to minimise their toxicities and maximise their antitumour activities for ovarian cancer treatment.

Animals↗
PubMed2006

Targeted therapies in gynecologic cancers.

With the rapid development of high-throughput techniques for identifying novel specific molecular targets in human cancer over the past few years, attention to targeted cancer therapy has dramatically increased. The term "targeted cancer therapy" refers to a new generation of drugs designed to interfere with a specific molecular target that is believed to play a critical role in tumor growth or progression, is not expressed significantly in normal cells, and is correlated with clinical outcome. There has been a rapid increase in the identification of targets that have potential therapeutic application. The clinical success of the small-molecule kinase inhibitor imatinib mesylate in chronic myeloid leukemia and gastrointestinal stromal tumors has accelerated the development of a new era of molecular targeted cancer therapy. The number of agents under preclinical and clinical investigation has grown accordingly. This emphasis on molecular biology and genetics has also resulted in significant changes in the treatment of gynecologic cancers. Several promising drugs targeting tyrosine kinases (EGFR and Her-2/Neu), mTOR, Raf kinase, proteasome, and histone deacetylases, as well as drugs affecting apoptosis and mitosis, are under development for clinical application. However, some clinical trials of p53 gene therapies and farnesyl transferase inhibitors have had limited success. In this review, we will focus on potential novel targets in gynecologic cancer and the development of targeted therapy and its clinical applications in gynecologic cancer.

Angiogenesis Inhibitors↗
PubMed2005

Phase II trial of imatinib mesylate in patients with recurrent platinum- and taxane-resistant epithelial ovarian and primary peritoneal cancers.

OBJECTIVES: To evaluate the efficacy and tolerability of imatinib mesylate (Gleevec; Novartis Pharmaceuticals, Basel, Switzerland) in patients with recurrent ovarian and primary peritoneal cancer. METHODS: This was an open-label, single-institution phase II trial. Patients were eligible if they had measurable platinum/taxane-resistant disease, received 2-4 prior treatment regimens, and over-expressed at least one imatinib target (c-Kit, PDGFR-beta, or c-Abl) by immunohistochemistry. Imatinib was administered orally at 600 mg daily for 6 weeks (one course) and was repeated in the absence of measurable progression. RESULTS: Sixteen enrolled patients were evaluable for toxicity and 12 for response. The median number of prior treatments was 4. A total of 29 courses were initiated. No complete or partial responses were documented during a median follow-up of 6.6 months. However, 4 (33%) of the 12 evaluable patients had stable disease lasting 3.8, 6.4, 7.5, and 8+ months. Expression of PDGFR-beta and c-Abl was seen in 15 (94%) and c-Kit in 8 (50%) patients' tumors. There was no relationship between best response (stable disease) and target expression. Adverse events were uncommon, with fatigue and nausea/vomiting being reported in 34% and 31% of cycles, respectively. Two patients underwent dose reduction for rash and edema (n = 1) and grade 3 neutropenia (n = 1). No grade 4 toxicity was observed. CONCLUSION: Imatinib mesylate was well tolerated but did not produce clinical responses in patients with previously treated metastatic ovarian and primary peritoneal carcinoma.

Aged↗
PubMed2005

Ovarian cancer, the coagulation pathway, and inflammation.

Epithelial ovarian cancer (EOC) represents the most frequent cause of death in the United States from a cancer involving the female genital tract. Contributing to the overall poor outcome in EOC patients, are the metastases to the peritoneum and stroma that are common in this cancer. In one study, cDNA microarray analysis was performed on fresh tissue to profile gene expression in patients with EOC. This study showed a number of genes with significantly altered expression in the pelvic peritoneum and stroma, and in the vicinity of EOC implants. These genes included those encoding coagulation factors and regulatory proteins in the coagulation cascade and genes encoding proteins associated with inflammatory responses. In addition to promoting the formation of blood clots, coagulation factors exhibit many other biologic functions as well as tumorigenic functions, the later including tumor cell proliferation, angiogenesis, invasion, and metastasis. Coagulation pathway proteins involved in tumorigenesis consist of factor II (thrombin), thrombin receptor (protease-activated receptors), factor III (tissue factor), factor VII, factor X and factor I (fibrinogen), and fibrin and factor XIII. In a recent study we conducted, we found that factor XII, factor XI, and several coagulation regulatory proteins, including heparin cofactor-II and epithelial protein C receptor (EPCR), were also upregulated in the peritoneum of EOC. In this review, we summarize evidence in support of a role for these factors in promoting tumor cell progression and the formation of ascites. We also discuss the different roles of coagulation factor pathways in the tumor and peritumoral microenvironments as they relate to angiogenesis, proliferation, invasion, and metastasis. Since inflammatory responses are another characteristic of the peritoneum in EOC, we also discuss the linkage between the coagulation cascade and the cytokines/chemokines involved in inflammation. Interleukin-8, which is considered an important chemokine associated with tumor progression, appears to be a linkage point for coagulation and inflammation in malignancy. Lastly, we review findings regarding the inflammatory process yielded by certain clinical trials of agents that target members of the coagulation cascade in the treatment of cancer. Current data suggest that disrupting certain elements of the coagulation and inflammation processes in the tumor microenvironment could be a new biologic approach to cancer therapeutics.

Journal Article↗
PubMed2005

Insulin-like growth factor binding protein 2 promotes ovarian cancer cell invasion.

BACKGROUND: Insulin-like growth factor binding protein 2 (IGFBP2) is overexpressed in ovarian malignant tissues and in the serum and cystic fluid of ovarian cancer patients, suggesting an important role of IGFBP2 in the biology of ovarian cancer. The purpose of this study was to assess the role of increased IGFBP2 in ovarian cancer cells. RESULTS: Using western blotting and tissue microarray analyses, we showed that IGFBP2 was frequently overexpressed in ovarian carcinomas compared with normal ovarian tissues. Furthermore, IGFBP2 was significantly overexpressed in invasive serous ovarian carcinomas compared with borderline serous ovarian tumors. To test whether increased IGFBP2 contributes to the highly invasive nature of ovarian cancer cells, we generated IGFBP2-overexpressing cells from an SKOV3 ovarian cancer cell line, which has a very low level of endogenous IGFBP2. A Matrigel invasion assay showed that these IGFBP2-overexpressing cells were more invasive than the control cells. We then designed small interference RNA (siRNA) molecules that attenuated IGFBP2 expression in PA-1 ovarian cancer cells, which have a high level of endogenous IGFBP2. The Matrigel invasion assay showed that the attenuation of IGFBP2 expression indeed decreased the invasiveness of PA-1 cells. CONCLUSIONS: We therefore showed that IGFBP2 enhances the invasion capacity of ovarian cancer cells. Blockage of IGFBP2 may thus constitute a viable strategy for targeted cancer therapy.

Cell Line, Tumor↗
PubMed2005

Ethics guidelines for research with the recently dead.

The objective of the multidisciplinary expert Consensus Panel on Research with the Recently Dead (CPRRD) was to craft ethics guidelines for research with the recently dead. The CPRRD recommends that research with the recently dead: (i) receive scientific and ethical review and oversight; (ii) involve the community of potential research subjects; (iii) be coordinated with organ procurement organizations; (iv) not conflict with organ donation or required autopsy; (v) use procedures respectful of the dead; (vi) be restricted to one procedure per day; (vii) preferably be authorized by first-person consent, though both general advance research directives and surrogate consent are acceptable; (viii) protect confidentiality; (ix) not impose costs on subjects' estates or next of kin and not involve payment; (x) clearly explain ultimate disposition of the body.

Death↗
PubMed2005

Frequent overexpression of STK15/Aurora-A/BTAK and chromosomal instability in tumorigenic cell cultures derived from human ovarian cancer.

The STK15 (also known as Aurora-A/BTAK) gene localized on chromosome 20q13 and encoding a centrosome-associated serine/threonine kinase is amplified and overexpressed in multiple human tumor cell types. Overexpression of this gene is involved in tumorigenic transformation, induction of centrosome duplication-distribution abnormalities, and aneuploidy in mammalian cells. To examine the potential role of STK15 in ovarian tumorigenesis, its mRNA and protein expression status were examined in cells grown in culture from 15 ovarian cancer specimens using semiquantitative RT-PCR and Western blot analysis. Normal ovarian surface tissues and the near diploid nontumorigenic breast epithelial cell line MCF10 were used as controls. The status of STK15 correlated with transformation-associated cellular phenotypes including tumorigenicity in nude mice, p53 expression level, and chromosomal ploidy. For chromosome ploidy analyses, FISH was carried out with direct fluorescence-labeled a-satellite probes for chromosome 3 and 17. STK15 mRNA was found overexpressed in 10 of the 15 ovarian cancer cell cultures. Five of these cell cultures revealed a truncated form of the STK15 protein with a molecular mass of 36 kDa. When tested for tumorigenicity in nude mice, 9 of the 10 cell cultures that overexpressed STK15 mRNA formed tumors in nude mice, while only one of the five cell cultures with no overexpression did. Cells overexpressing STK15 mRNA showed significant correlation with chromosome 3 polysomy. Six of the 13 (46%) cell cultures analyzed for p53 expression revealed overexpression of p53 and five of these six (83%) also overexpressed STK15. Four of the remaining seven cultures (57%) with overexpression of STK15 revealed minimal or no expression of p53. These results demonstrate that overexpression of STK15 significantly correlates with nude mice tumorigenicity and chromosomal aneuploidy in human ovarian cancer cells grown in vitro. Additionally, cells overexpressing STK15 also revealed frequent coordinate loss of wild-type p53 function manifested either as highly expressed intense staining reflective of a mutant form of p53 or almost complete absence of p53 staining. Overexpression of STK15 with coordinate loss of wild-type p53 function thus appears to play an important role in ovarian tumorigenesis and offers a novel molecular target in designing effective therapy of human ovarian cancer.

Aneuploidy↗
PubMed2004

An assessment of the utilization of complementary and alternative medication in women with gynecologic or breast malignancies.

PURPOSE: To describe and assess the current utilization of complementary and alternative medicines (CAMs) in women with a diagnosis of either gynecologic or breast cancer and evaluate their reasons for use. PATIENTS AND METHODS: This study included 250 female patients from the Multidisciplinary Breast Center and 250 patients from the Gynecologic Oncology Center of The University of Texas M.D. Anderson Cancer Center (Houston, TX). Patients were selected by having an odd-numbered medical record number, and they were contacted before their clinic visit. The goals of the study were explained, and verbal consent was obtained. Patients who agreed to participate were asked to bring a written list and the medication bottles of all over-the-counter prescriptions and CAMs with them to clinic. In clinic, the investigator obtained a written informed consent and administered the survey. All patients and surveys were assessable. RESULTS: The most frequently used herbal products and megavitamins/minerals were identified from the patient medication histories. Overall, we found the proportion of patients using CAM to be 48% (95% CI, 44% to 53%; 241 of 500 patients). CAM use was related to patients' educational status: 62% had postgraduate degrees, 50% had college degrees, 56% had some college, and 33% had a high school education or less. Also, among patients using CAMs, only 53.5% had spoken to a healthcare provider regarding CAM therapy. CONCLUSION: The use of CAM is common among women with cancer. Studies need to be conducted to establish if there are any potential drug interactions and/or therapeutic benefit of CAM products. Moreover, there is a need to educate patients and healthcare providers on appropriate and safe use of CAM products.

Adult↗
PubMed2004

Proteomics in cancer screening and management in gynecologic cancer.

Biomarkers are used routinely for population screening, disease diagnosis and prognosis, monitoring of therapy, and prediction of therapeutic response. Unfortunately, most biomarkers have low sensitivity and specificity and little predictive value. Novel techniques for better screening and early diagnosis of ovarian cancer are urgently needed. Proteomics, the study of the cellular proteins and their activation states, integrates some fundamental techniques, including high-throughput protein purification and profiling, genomic and proteomic databases, and mass spectrometry. In oncology, proteomics will contribute greatly to our understanding of gene functions in tumor development and provide information in clinical applications. This article reviews proteomic techniques and their potential applications in gynecologic cancer screening and management.

Biomarkers, Tumor↗
PubMed2004

Efficacy and safety of liposomal anthracyclines in phase I/II clinical trials.

Preclinical studies have established the pharmacologic advantages of liposomal anthracyclines, including pharmacokinetic profiles after bolus dosing that resemble continuous infusion of conventional anthracyclines, increased drug concentrations in tumor cells compared with the surrounding tissues, and reduced toxicity relative to conventional anthracycline treatment. Based on these studies, many phase I and phase II clinical trials were conducted to assess the safety and potential activity of liposomal anthracyclines in the management of both solid and hematologic tumors. These studies provided valuable insight into the safety of pegylated liposomal doxorubicin (Doxil/Caelyx [PLD]), nonpegylated liposomal doxorubicin (Myocet [NPLD]), and liposomal daunorubicin (DaunoXome [DNX]) over a range of doses, either as single-agent therapy or in combination with other cytotoxic agents. Other liposomal anthracyclines in development may be well tolerated but their activity remains to be elucidated by clinical trials. The available data also suggest that liposomal anthracyclines have activity not only against tumor types with known sensitivity to conventional anthracyclines, but also potentially for tumors that are typically anthracycline-resistant. Despite the availability of clinical data from a wide variety of tumor types and patient populations, further studies of liposomal anthracycline therapy are needed to fully establish their safety, efficacy, and dosing in the treatment of these patients.

Antibiotics, Antineoplastic↗
PubMed2004

Novel agents in epithelial ovarian cancer.

The gold standard chemotherapy for previously untreated patients with ovarian cancer is currently a combination of taxane and platinum. However, most patients still suffer relapse, and less than 20% of the patients with stage III or IV disease survive long term. With more advanced technology, newer cytotoxic agents have been identified and are currently being tested in patients with ovarian cancer. Recent advances in the understanding of ovarian cancer biology have also led to the identification of multiple molecular targets that may soon change the standard treatment of ovarian cancer. Several of these targeted agents have entered clinical trials. Small molecular-weight inhibitors, monoclonal antibodies, antisense therapy, and gene therapy are all being evaluated alone and in combination with cytotoxic chemotherapy. Several of these cytotoxic and targeted therapies are reviewed here. Ultimately, the success of ovarian cancer therapy lies not just in the availability of new agents but in the ability to identify patients with biomarkers that may predict their response to these agents.

Antineoplastic Agents↗
PubMed2003

Pilot study of Flt3 ligand comparing intraperitoneal with subcutaneous routes on hematologic and immunologic responses in patients with peritoneal carcinomatosis and mesotheliomas.

PURPOSE: This study compared the clinical toxicity and hematological effects of i.p. and s.c. administration of fms-like tyrosine kinase-3-ligand (Flt3-L; Amgen, Thousand Oaks, CA), a truncated glycoprotein that increases dendritic cells (DCs) and monocytes. EXPERIMENTAL DESIGN: Patients with peritoneal carcinomatosis or mesothelioma were randomly assigned to treatment with Flt3-L (25 micro g/kg, maximum 1500 micro g), i.p. or s.c., days 1-5 and 8-12, then changed to the alternative route at 4 weeks. Treatment was continued s.c. or i.p. at 8 weeks. RESULTS: Fifteen patients (14 evaluable) were randomized to receive i.p. (n = 8) or s.c. (n = 7) injections. Their median age was 55 years (range, 40-68 years). Primary tumors were as follows: ovarian/peritoneal cancer (n = 9); gastrointestinal cancer (n = 2); and mesothelioma (n = 4). Treatment was well tolerated without serious toxicity (24 i.p. cycles; 32 s.c. cycles). Treatment (i.p. or s.c.) resulted in significant increases in WBCs (WBC, monocytes, and Lin(-)DR(+) DCs), and platelets (during washout). Both interleukin (IL)-12(p70) and IL-10 were secreted by monocyte-derived DCs after in vitro exposure to maturation factors. Increased IL-12 versus IL-10 secretion responses and higher proportions of the CD11c(+) DC subset in post-Flt3-L specimens suggested a maturational shift toward the monocyte-derived DC phenotype had occurred. Three patients (2 with mesothelioma and 1 with gastrointestinal cancer) had stable disease for 8, 8, and 12+ months, respectively. CONCLUSIONS: Flt3-L, administered either i.p. or s.c., is well tolerated and produced similar increases in monocytes, DCs, and platelets. DCs from peripheral blood and peritoneal fluids showed cell surface phenotypic and cytokine maturational responses to activation stimuli. These findings suggested that Flt3-L, in combination with suitable activating agents, could be developed further in patients with epithelial ovarian cancer.

Adjuvants, Immunologic↗
PubMed2003

A phase II study of intravenous exatecan mesylate (DX-8951f) administered daily for 5 days every 3 weeks to patients with advanced ovarian, tubal or peritoneal cancer resistant to platinum, taxane and topotecan.

BACKGROUND: DX-8951f is a water-soluble camptothecin derivative with greater in vivo and in vitro activity than topotecan or irinotecan. The objectives of this phase II study were to determine the antitumor activity, safety and pharmacokinetic profile of DX-8951f administered intravenously for five consecutive days, every 3 weeks in patients with advanced ovarian, tubal and peritoneal cancer resistant to platinum, taxane and topotecan. METHODS: Enrolled in the study at The University of Texas M. D. Anderson Cancer Center were 16 patients with measurable cancer resistant to platinum, taxane and topotecan. All 16 patients were assessable for safety and 15 for efficacy analyses. Treatment consisted of a daily infusion of DX-8951f at 0.3 mg/m(2) per day (except for one minimally pretreated patient who started at 0.5 mg/m(2) per day) over 30 min for five consecutive days every 3 weeks. The pharmacokinetic and excretory profiles of DX-8951, the anhydrous form of DX-8951f, were also characterized. RESULTS: Disease was stable in 7 of 16 patients (44%) (4 minor response and 3 stable disease). The median time to tumor progression was 43 days (95% CI 37-92 days). The median overall survival was 117 days (95% CI 90-279 days). The main toxic effect was neutropenia and leukopenia with 50% of patients experiencing grade 3 or 4 neutropenia and leukopenia. One episode of neutropenic fever was observed. Grade 3 or more anemia and thrombocytopenia were seen in 25% and 13% of patients, respectively. Grade 3 nonhematologic side effects included nausea (25% of patients) and fatigue (19%). Other side effects were not more than grade 2, and included gastrointestinal dysfunction, stomatitis, dermatitis, alopecia, liver dysfunction and drug fever. DX-8951 displayed linear pharmacokinetic characteristics at the doses administered. The average plasma clearance, total volume of distribution, and terminal elimination half-life were 2.1 l/h per m(2), 20 l/m(2) and 9.5 h, respectively. CONCLUSIONS: DX-8951f administered parenterally as a single agent daily at a dose of either 0.5 or 0.3 mg/m(2) per day for 5 days is feasible in patients with advanced ovarian, tubal and peritoneal cancer resistant to platinum, taxane and topotecan. Although no responses were observed, a significant number of patients had stable disease with a decrease in CA-125 levels. In this heavily pretreated population, DX-8951f has clinically relevant hematologic and gastrointestinal toxicities in about 25% of patients. DX-8951 appeared to have linear pharmacokinetic characteristics on the basis of multiple administrations.

Adult↗
PubMed2003

Phase II trial of irinotecan in patients with metastatic epithelial ovarian cancer or peritoneal cancer.

PURPOSE: To evaluate the efficacy and toxicity of irinotecan in patients with metastatic platinum-resistant or platinum-refractory epithelial ovarian cancer or primary peritoneal cancer. PATIENTS AND METHODS: Thirty-one patients with measurable disease were enrolled in our study at The University of Texas M.D. Anderson Cancer Center. Twenty-five of these patients were treated with irinotecan at a dose of 300 mg/m2 intravenously for 90 minutes every 3 weeks; the remaining six patients were treated with 250 mg/m2 because their age was greater than 65 years. Median age was 57 years (range, 38 to 74 years). The majority (84%) had a Zubrod performance status of 0. All patients were evaluated for irinotecan toxicity, and 29 (94%) were evaluable for response. RESULTS: The overall response rate was 17.2%. One patient (3%) had a complete response, four (14%) had partial responses, 14 (48%) had stable disease, and 10 had (35%) disease progression. Median progression-free survival was 2.8 months (range, 1.1 to 16 months), median duration of response was 1.4 months (range, 0.7 to 10.1 months); median survival from primary diagnosis was 24.3 months (range, 6.5 to 85.7 months); and median survival from initiation of irinotecan was 10.1 months (range, 2.3 to 34 months). Major toxicities included fatigue (16 patients), neutropenia (11 patients), diarrhea (nine patients), nausea (10 patients), and anorexia (seven patients). Eleven patients required dose reductions because of these toxicities. No treatment-related deaths occurred. CONCLUSION: Irinotecan has moderate efficacy and substantial toxicity in patients with metastatic platinum-resistant or platinum-refractory epithelial ovarian or primary peritoneal cancer.

Adenocarcinoma, Clear Cell↗
PubMed2003

Proteomic identification of heat shock protein 70 as a candidate target for enhancing apoptosis induced by farnesyl transferase inhibitor.

Farnesyl transferase inhibitors (FTIs) are novel antitumor drugs with clinical activity. FTIs inhibit cell growth not only by preventing direct Ras farnesylation but also through a Ras-independent pathway. Proteomics has been shown to be a powerful tool to monitor and analyze molecular networks and fluxes within the living cells and to identify the proteins that participate in these networks upon perturbation of the cellular environment. To observe early and dynamic protein changes in the cellular response to FTI in ovarian cancer cells, total proteins were extracted from 2774 cells treated or not with 10 microM manumycin, an FTI, for 3, 6 and 16 h. The proteins in the cells that were differentially expressed following treatment with manumycin for 3, 6 and 16 h were noted by two-dimensional electrophoresis and further identified by peptide mass fingerprinting as stress proteins. Both heat shock protein 70 (HSP70) and altered HSP70 were significantly up-regulated as early as 16 h in 2774 cells after exposure to manumycin. Since HSP70 plays an important role in protecting cells under stress, we treated the 2774 cells with the HSP inhibitor quercetin in combination with FTI. Quercetin dramatically enhanced the manumycin-mediated apoptosis in 2774 cells. Inducible HSP70 by manumycin in surviving ovarian cancer cells was also inhibited by quercetin as demonstrated by enzyme-linked immunosorbent assay. The inhibition of HSP70 by quercetin was correlated with enhancement of manumycin-induced mediated apoptosis in 2774 cells. The inhibition of HSP70 by 50 microM quercetin was also correlated with a decreased expression of procaspase-3 and enhancement of specific cleavage of poly (ADP-ribose) polymerase into apoptotic fragment in 2774 cells treated with manumycin. The interaction between the HSP70 inhibitor and FTI confirms the functional significance of the up-regulation of HSP70 as a protective mechanism against FTI-induced apoptosis and provides the framework for combination treatment of ovarian cancer.

Alkyl and Aryl Transferases↗
PubMed2003

Vulvar Langerhans cell histiocytosis: a case report and review of the literature.

BACKGROUND: Langerhans cell histiocytosis (LCH) of the female genital tract is rare. Only, seven cases of primary vulvar LCH have been previously reported in the medical literature. We describe an additional case of LCH in which the disease was confined to the vulva. CASE: A 33-year-old gravida 0, para 0 Ethiopian woman presented with a nodular lesion on her left vulva. The lesion was biopsied, and the results were consistent with LCH. A metastatic workup did not reveal any evidence of disease beyond the vulva. The patient was initially treated with radiotherapy to the vulva. She was diagnosed with recurrent disease in the vulva 21 months after the completion of radiotherapy. At that time, she underwent a wide local excision. Five months later, we found a lesion on her right labium majus that was consistent with a recurrence. The patient's vulva was treated with a higher dose of radiotherapy than it had been the first time. Six months later the patient again experienced a local recurrence. She underwent a wide radical vulvar excision of diffuse bilateral lesions and was free of disease for approximately 3 months, after which she experienced another recurrence and underwent treatment with thalidomide. Within 2 months of starting thalidomide therapy, the patient experienced resolution of her symptoms and of her vulvar lesions. CONCLUSIONS: Primary LCH of the vulva is very rare. Its etiology and pathophysiology, as well as the most effective modes of therapy, remain elusive. We propose that thalidomide is a useful alternative for patients with this disease.

Adult↗