Terminal Ovarian Cancer Research Articles

Analysis of transferrin in urine in patients with bladder cancer using nanobodies

It is known that the saturation ratio of transferrin (Tf) with iron in human blood is an important clinical parameter. Specific antibodies can be used to analyze subtle changes in the relative abundance of different forms of transferrin potentially associated with a pathological process. Recently, the authors of this study were able to obtain and characterize highly specific single-domain antibodies (nanobodies) that predominantly recognize the iron-saturated (holo-Tf) or iron-unsaturated (apo-Tf) form of transferrin. In this work, under conditions closer to physiological than in previous experiments, we further demonstrated that these unique nanobodies have extremely high differential binding specificity for different forms of Tf in different human biological fluids. Using these nanobodies, we were able to analyze for the first time the relative abundance of transferrin forms in urine samples from patients with bladder cancer (BC). We have shown that an increase in the concentration of total Tf in urine samples normalized for creatinine is associated with the degree of progress and growth of malignancy of BC. In the samples of healthy donors and in the early stages of BC (G1), Tf is detected in much smaller amounts (compared to later stages) and only with additional concentration of the studied samples. For most of the studied urine samples from BC patients, it is expected (as previously shown in the case of Tf in the blood of terminal ovarian cancer patients) that the concentration of apo-Tf is clearly higher than holo-Tf, especially in the case of the most advanced muscle-invasive BC. It was a surprise for us that approximately equal amounts of apo-Tf and “holo-Tf” were found in the urine samples of some patients with BC. We hypothesized that the “holo-Tf” fraction in this case can be largely represented by “secondary complexes” formed by apo-Tf in combination with ions other than Fe3+, which accumulate in the urine of some cancer patients and are able to bind to apo-Tf, changing its conformation towards holo-Tf. Using inductively coupled plasma ionization mass spectroscopy (ICP-MS), we obtained the first results confirming our hypothesis. The “holo-Tf” preparation in these urine samples was found to be highly enriched in zinc and nickel. Also in this preparation, a relative enrichment in cadmium is observed, but it is present in much lower concentrations. The data obtained indicate that the nanobody used, recognizing predominantly the iron-saturated form of transferrin (holo-Tf), is also capable of binding transferrin in association with other metal ions that are different from iron. This ability could potentially open up new possibilities in studies of the relative abundance of various metal ions in association with transferrin in human biological fluids in normal and pathological conditions.

Analysis of Transferrin in the Urine of Patients with Bladder Cancer Using Nanobodies.

It is known that the saturation ratio of transferrin (Tf) with iron in human blood is an important clinical parameter. Specific antibodies can be used to analyze subtle changes in the relative abundance of different forms of transferrin potentially associated with a pathological process. Recently, the authors of this study were able to obtain and characterize highly specific single-domain antibodies (nanobodies) that predominantly recognize the iron-saturated (holo-Tf) or iron-unsaturated (apo-Tf) form of transferrin. In this work, under conditions closer to physiological than in the previous experiments, we further demonstrated that these unique nanobodies have extremely high differential binding specificity for different forms of Tf in different human biological fluids. Using these nanobodies, we were able to analyze for the first time relative abundance of the transferrin forms in urine samples from the patients with bladder cancer (BC). We have shown that increase in the concentration of total Tf in the urine samples normalized for creatinine is associated with the degree of progress and growth of malignancy of BC. In the samples of healthy donors and in the early stages of BC (G1), Tf is detected in much smaller amounts (compared to the later stages) and only with additional concentration of the studied samples. For most of the studied urine samples from the BC patients, it is expected (as previously shown in the case of Tf in the blood of terminal ovarian cancer patients) that the concentration of apo-Tf is clearly higher than holo-Tf, especially in the case of the most advanced muscle-invasive BC. It was a surprise for us that approximately equal amounts of apo-Tf and holo-Tf were found in the urine samples of some patients with BC. We hypothesized that the holo-Tf fraction in this case could be largely represented by the "secondary complexes" formed by apo-Tf in combination with ions other than Fe3+, which accumulate in the urine of some cancer patients and are able to bind to apo-Tf, changing its conformation towards holo-Tf. By using inductively coupled plasma mass spectroscopy (ICP-MS), we obtained first results confirming our hypothesis. Preparation of the holo-Tf in these urine samples was found to be highly enriched in zinc and nickel. Also, relative enrichment in cadmium has been observed in this preparation, but at much lower concentrations. The obtained data indicate that the used nanobody, while recognizing predominantly the iron-saturated form of transferrin (holo-Tf), is also capable of binding transferrin in association with other metal ions that are different from iron. This ability could potentially open up new possibilities for investigation of relative abundance of various metal ions in association with transferrin in human biological fluids in normal and pathological conditions.

Ascites Volumes and the Ovarian Cancer Microenvironment.

Epithelial ovarian cancer is the leading cause of death from gynecologic malignancy among women in developed countries. Epithelial ovarian cancer has a poor prognosis, due to the aggressive characteristics of the disease combined with the lack of effective therapies. Options for late-stage ovarian cancer are limited and invasive, especially once malignant ascites develops. Malignant ascites, a complication observed in terminal ovarian cancer, significantly contributes to poor quality of life and to mortality. Excess accumulation of fluid in the peritoneal cavity occurs due to a combination of impaired fluid drainage and increased net filtration, mostly due to increasing intraperitoneal vascular permeability. Here we applied non-invasive magnetic resonance imaging (MRI) and spectroscopic imaging (MRSI) of syngeneic mouse tumors in vivo, and high-resolution 1H MRS of mouse tumor extracts, to characterize the relationship between ascites volumes and the vasculature and metabolism of an experimental model of ovarian cancer. Differences were observed in the tumor vasculature and metabolism in tumors based on ascites volumes that provide new insights into the development of this condition.

Davida Coady: humanitarian paediatrician, political activist, and recovering alcoholic

As a paediatrician and then, later in her career, as an addiction treatment specialist, Davida Coady’s mission in life was to do “the greatest good for the greatest number of...

Abstract 324: Pantethine, a new therapeutic approach against ovarian cancer.

Abstract Ovarian cancer is the leading cause of death from gynecologic malignancy among women in developed countries with an estimated incidence of 205,000 cases worldwide per year, resulting in 125,000 deaths. Although the prognosis in cases detected at early stage is quite favorable, the vast majority of cases are diagnosed at an advanced stage, when five-year survival rates are only 30-40%. The poor prognosis of ovarian cancer is due to a combination of the aggressive characteristics of the disease and a lack of effective therapy, further compounded by late detection of the disease and resistance of most tumors to current treatments. Metastases and malignant ascites, a devastating condition that significantly contributes to poor quality of life and mortality, are complications frequently observed in terminal ovarian cancer. New therapeutic strategies exploiting novel targets are urgently needed to minimize morbidity and improve survival rates for ovarian cancer patients. In the present study, we applied non-invasive MRI to determine the use of pantethine as a therapeutic agent in an orthotopic model of ovarian cancer. Pantethine is the stable disulfide form of pantetheine, a derivative of vitamin B5; it is the precursor of coenzyme A. In a mouse model, pantethine has been shown to prevent the perivascular inflammation associated with cerebral malaria (1) and to inhibit cell transendothelial migration (Gharib B, unpublished data). To detect the effect of pantethine on ovarian cancer progression, metastases, and ascites build-up, we used an orthotopic model in which the relevant tumor physiological environment is maintained, and that frequently result in metastases and malignant ascites. OVCAR3 human epithelial ovary adenocarcinoma cells were used in the present study. The orthotopic implantation was performed by surgically transplanting a piece of OVCAR3 tumor tissue on the ovary of severe combined immunodeficient female mice. We started the treatment 4 weeks post-implantation, when the tumors were approximately 100 mm3 with a daily i.p. injection of pantethine at a dose of 750 mg/kg. Under these conditions, no side effects were observed. A control group was injected daily with saline. Tumor growth was followed weekly non-invasively by MRI on a 4.7T spectrometer. Slower tumor growth was observed in the treated group. Interestingly, when we sacrificed the mice after 4 weeks of treatment, we observed liver metastases in 6 out of 7 control mice, but only in 3 out of 7 treated mice, lungs metastases in 2 out of 7 control mice, and 0 out of 7 treated mice and finally, ascites in 6 out of 7 control mice, and 2 out of 7 treated mice. Our study identifies pantethine as a new promising drug against ovarian cancer, showing effects on tumor progression, metastases occurrence, and ascites formation. (1) Penet MF et al. PNAS 105:1321-6, 2008. This work was supported by a Career Award to M-FP from NIH P50CA103175, The HERA Foundation, and The Honorable Tina Brozman Foundation. Citation Format: Marie-France Penet, Silvana Canevari, Franca Podo, Max de Reggi, Bouchra Gharib, Zaver M. Bhujwalla. Pantethine, a new therapeutic approach against ovarian cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 324. doi:10.1158/1538-7445.AM2013-324

The Case of the Disappearing Plaintiffs: Robert Baxter et al vs. State of Montana

In December, 2008, Montana District Court Judge Dorothy McCarter ruled Montana citizens who are competent and terminally ill have legal right to assisted suicide based on the State's constitutional recognition of individual privacy and human dignity. The case was launched by Compassion and Choices, euthanasia/assisted suicide advocacy group.The most interesting aspect of the Baxter case concerns the four physician plaintiffs: Stephen Speckart, MD, C. Paul Loehnen, MD, Lar Autio, MD, and George Risi Jr., MD.All four stated Montana's homicide statutes had deterred them from providing the kind of they believed their patients needed. In virtually identical passages, their affidavits each stated the deterrent effect of Montana's homicide statutes had sometimes resulted in patients...dying tortured deaths.Turn now to the story of Janet Murdock, 67 year old woman with terminal ovarian cancer. Her own physician refused to write prescription for lethal medication. Compassion and Choices held press conference in the hope that Janet's appeal today for aid in dying will prompt willing physician to come forward and contact Compassion and Choices. But no physician came forward, and Janet Murdock died of physical deterioration caused by ovarian cancer on 14 June, 2009. Janet Murdock lived in Missoula, city with population of about 64,000. So did the four plaintiff physicians. They all believed they had professional obligation to relieve suffering, and this professional obligation justified assisted suicide. All four complained they had been prevented from assisting in suicide because of Montana's homicide statutes. All four had gone to court to help to overturn those statutes so they could provide assisted suicide, so no one would have to endure what they called a tortured death. Even after the April news conference, not one of them was willing to give Janet Murdock the lethal prescription she was seeking. Having joined Compassion and Choices in the battle to legalize assisted suicide in Montana, they seem to have gone missing in action just when they were most needed.Let us suppose one of the four physician plaintiffs did see her. Even if the views on assisted suicide expressed in his affidavit remained unaltered, and even if he was not concerned about the ethical opinions of his colleagues or the possibility of being prosecuted or sued, it does not follow he would provide her with lethal prescription. Depending upon his assessment, he might - or he might not.This point is often overlooked, but it is important. Even health care workers willing to provide assisted suicide in some circumstances may, for reasons of conscience, be unwilling to provide it in others. Moreover, their willingness may change over time. This is true of abortion, and there is no reason to think it is not also true of euthanasia, assisted suicide or other morally controversial procedures.

The Trinity River Plays (review)

Reviewed by: The Trinity River Plays Colleen Daniher The Trinity River Plays. By Regina Taylor. Directed by Ethan McSweeny. Dallas Theater Center and Goodman Theatre, Goodman Theatre, Chicago. 16 January 2011. The search for rootedness links the three plays that comprise Regina Taylor's The Trinity River Plays: Jarfly, Rain, and Ghoststory. Centered on the psychic and physical separation from and eventual return of Iris Spears to her family, Taylor's trilogy uses roots as a central metaphor to understand the cyclical yet sustaining role that family plays in the life of an individual. At a combined running time of over three hours, Taylor's digging spreads itself wide, but perhaps not deep enough. And yet, in its refusal to conceptualize "roots" beyond the myopic world of the Spears family unit, the trilogy speaks to a political present that is increasingly unwilling to address race as a framework that continues to structure everyday life, including the everyday experience of family relations. Set in the declining years of the civil rights and Black Power movements and in the long shadow of Senator Daniel Patrick Moynihan's pathologizing condemnation of the black family in 1965, the Click for larger view View full resolution Karen Aldridge (Iris) in The Trinity River Plays. (Photo: Brandon Thibodeaux.) [End Page 642] Click for larger view View full resolution Karen Aldridge (Iris), Jacqueline Williams (Daisy), Jefferson A. Russell (Ray Earl), and Christiana Clark (Jasmine) in The Trinity River Plays. (Photo: Brandon Thibodeaux.) Goodman production staged a strange elision of race politics, even as it took the black matriarchal family as its central focus. What resulted was a production caught between performing a multigenerational story of black women's struggle and continued survival and insisting that this story transcend race. As staged by director Ethan McSweeny, this latest offering from Taylor, one of the nation's leading African American playwrights and performers, thus provoked critical reflection on the influence of colorblind thinking on contemporary African American theatre. The three plays follow Iris (Karen Aldridge) for seventeen years, from the morning of her seventeenth birthday in 1978 (Jarfly) to her return visit home to Oak Cliff, Dallas in 1995 (Rain). Upon the discovery of her mother Rose's diagnosis of terminal ovarian cancer, Iris's visit turns into an extended stay that carries over into the aftermath of her mother's passing (Ghoststory). Two major occurrences punctuate the extended narrative as it unfolds over the three plays: the rape of Iris by her uncle Ray Earl on her seventeenth birthday in Jarfly, and the aforementioned diagnosis of Iris's mother with advanced-stage ovarian cancer seventeen years later in Rain. The last play in the trilogy, Ghoststory, sees Iris reconcile with her ex-husband Frank, as well as come to terms with her mother's death with the help of her Aunt Daisy and cousin Jasmine. The seventeen-year chronology of the plays reflects the seventeen-year lifespan of the cicada, or jarfly, whose symbolic death and rebirth is mapped onto the "bug-eyed" Iris. Guided by Taylor's script, the Goodman production exhibited the realist aesthetics of the self-contained domestic drama; the set design by Todd Rosenthal was meticulously detailed, from the downstage garden in which Iris and Rose actually dig up soil, to the unanswered whistling kettle that signaled the decline of Iris's mother. This realism highlighted the almost tyrannical ordinariness with which Taylor and McSweeny imbued the Spears family. As necessitated by the physical environment, Aunt Daisy (Jacqueline Williams) was forever cooking or washing in the kitchen, while Rose (Penny Johnson Jerald) seemed to spend her days playing the piano and gardening. While the sustained focus on domestic rituals effectively established the Spears family as one "like any other," the relentlessness of the generic quotidian threatened to overshadow what was most compelling about the Goodman production—namely, the particular ways in which race informed the Spears family's relations and traumas. Indeed, the most moving moments of the evening occurred when the production engaged the cultural [End Page 643] specificity of its themes, as, for example, when the gospel rounds punctuating the scenic transitions sounded the bond among Iris, her mother, her cousin, and...

Fearlessly exploring the other: the role of drama in medical training

Drama has been used as a medium for instruction within medical education, with particular focus on illness-centred performance.1 At the University of California, Davis, faculty from the Department of English...

Influence of nursing intervention on curative effects of patients with terminal ovarian cancer when cured by radioheating combined with IPHP

Objective To know the influence of nursing intervention on curative effects of patients with terminal ovarian cancer when cured by radioheating combined with IPHP. Methods Divided 26 patients with terminal ovarian cancer when cured by radioheating combined with IPHP into the control group and the in-tervention group randomly, there were 13 cases in each group. Normal nursing cares and nursing intervention was carried out in each group respectively. Compared the indicence rate of advers reaction, depress and anxiety between the two groups. Results There were no significant difference between the two groups about the inci-dence rate of advers reaction, the degree of depress and anxiety in the intervention group were significant lower than those of in the control group. Conclusions Nursing intervention can effective release the depress and anxiety of patients with terminal ovarian cancer, and then promote their quality of life. Key words: Radioheating; Hyperthermic intraperitoneal chemotherapy perfusion; Ovarian can-cer, Nursing

Two cases of terminal ovarian cancer treated with Cell-free and Concentrated Ascites Reinfusion Therapy (CART)

Two cases of terminal ovarian cancer treated with Cell-free and Concentrated Ascites Reinfusion Therapy (CART)

The effect of total parenteral nutrition on the survival of terminally ill ovarian cancer patients

Objectives. Total parenteral nutrition (TPN) for terminal ovarian cancer patients remains controversial. In this study, we compared survival from time of terminal intestinal obstruction (TIO) diagnosis in patients who received TPN versus those who did not. Methods. A historical cohort of 55 patients with stage IIIC/IV epithelial ovarian cancer hospitalized for TIO between 1994 and 2002 was studied. All patients were previously treated with paclitaxel/platinum following cytoreductive surgery. Exposure was administration of TPN after TIO. The primary outcome was survival from TIO diagnosis to death. Number of chemotherapy cycles completed after TIO diagnosis, major complications of TPN, and demographics were measured. Survival analysis was performed using Kaplan–Meier methods. Results. The median survival from time of TIO diagnosis was 72 days (range 16–485) for patients receiving TPN and 41.0 days (range 4–133) for those not receiving TPN ( P = 0.05), but no difference in survival was observed when adjusting for chemotherapy. Overall survival [median 23 (range 6–67) vs. 35 months (range 8–67), P = 0.03] was shorter for the TPN group. Demographic data were similar in both groups. Patients receiving TPN after obstruction were more likely to undergo concurrent chemotherapy (64 vs. 26%, P = 0.004). One major TPN-related complication was found. Conclusions. Ovarian cancer patients with TIO receiving TPN had a median survival benefit of 4 weeks. This benefit decreased when patients were treated with concurrent chemotherapy. Issues of cost, quality of life, and human values need to be investigated to assess the full impact of TPN in this patient population.

Understanding health information, communication, and information seeking of patients and consumers: a comprehensive and integrated model

Understanding health information, communication, and information seeking of patients and consumers: a comprehensive and integrated model

Leaving Liza

This is Chapter Thirteen of Leaving Liza, a novel about life, death, love, friendship, jealousy and lesbian ex-lovers. In the novel, six women are spending the weekend at a beach house in Long Island's Hamptons, where they have gathered to be with their friend Liza, who is battling terminal ovarian cancer. Liza's lover, Jill, has agreed to the house party and helped plan the guest list. But, as she smolders with resentment at the attention Liza is getting and the depth of the women's friendships, she begins to come unraveled. After a severe asthma attack that requires an emergency room visit the day before, Jill conducts a seance, purporting to have contacted another of Liza's ex-lovers, who died a few months earlier. Now, on this last night of the house party, she lets Liza and her friends know what she's really feeling. The editors have asked me to add some “commentary” on the questions this story raises about the roles of ex-lovers. I would hope the scene reflects some of the tensions that can occur when ex-lovers choose to remain friends, particularly when those bonds provoke profound jealousy in both current and ex-lovers. For many of us, the job of assuaging and reassuring the current lover while maintaining intimate friendships with an ex-lover is simply too exhausting and prickly to endure. For others, it is worth the struggle. Liza and her friends clearly think it is. But at what point, they all wonder at this house party, does their hunger for honesty and their anger at being insulted and manipulated become more important than keeping the peace, and possibly their friendship with Liza? Perhaps only Liza's death will free them from this compromising coexistence.

Symptomatic benefit of supplemental oxygen in hypoxemic patients with terminal cancer: The use of the N of 1 randomized controlled trial

The symptomatic effects of oxygen on the dyspnea of terminally ill cancer patients have not been clearly established. Therefore, the decision to administer oxygen is frequently made on an individual basis. We report on the use of N of 1 randomized clinical trial to compare the symptomatic benefit of respiratory failure due to terminal ovarian cancer. A 53-yr-old female patient underwent 6 randomized double-blind crossover trials between oxygen 5 L/min delivered by mask and air 5 L/min delivered by mask. Each treatment period lasted 5 min. The mean saturation of oxygen during the baseline period was 84% ± 3%, versus 84% ± 4% on air ( P, NS) and 94% ± 4% on oxygen ( P < 0.001). The mean visual analogue scale (VAS) for dyspnea was 77 ± 4 during the baseline period as compared to 51 ± 7 after air ( P < 0.001), and 40 ± 5 after oxygen ( P < 0.001). The patient and the investigator chose oxygen blindly in 5 of 5 cases, air in 0 and 1 case, and no choice was made in 1 and 0 case, respectively. In 4 cases the patient considered the difference between oxygen and air to be of “much importance,” and in one case to be of “moderate importance.” No significant treatment, period, or interaction between period and treatment was detected for the difference in the VAS. We conclude that oxygen was significantly better than air for symptomatic improvement in this patient. The N of 1 technique is a simple and reliable method for the assessment of individual patients' response to oxygen.

Palliation of small bowel obstruction by percutaneous gastrostomy in patients with progressive ovarian carcinoma

Percutaneous gastrostomy is a useful palliative technique for treatment of patients with bowel obstructions in advanced ovarian carcinoma. A description of the technique is presented along with a review of ten cases in which the procedure was used at The University of Texas M.D. Anderson Hospital and Tumor Institute at Houston. In all patients, the procedure was well tolerated and associated with little morbidity. In applicable cases, percutaneous gastrostomy appears to be superior to both nasogastric suction and operative gastrostomy for palliation of small bowel obstruction in terminal ovarian cancer.