Download (.pdf) After Sontag: Reclaiming Metaphor
Genre, Vol. 44, No. 3 Fall 2011a
Susan Sontag’s Illness as Metaphor and AIDS and Its Metaphors critiqued the use of metaphoric language, particularly... more Susan Sontag’s Illness as Metaphor and AIDS and Its Metaphors critiqued the use of metaphoric language, particularly military metaphors of invasion and battle, to describe illness experiences. Metaphors generate explanatory narratives, just as stories often use a resonant metaphor as shorthand for theme. Metaphors and narratives can suggest reductive or stereotypical ways of imagining illness, disability, and other experiences of embodiment. Rather than an end to metaphoric framing of illness, however, the agency to make metaphors needs to be conferred to a larger constituency that always includes the patient. The author’s first-person ovarian cancer narrative illustrates that not having the capacity to make metaphors for one’s embodied experiences can mean late diagnosis; the dearth of effective public metaphors for imagining some internal organs, such as the ovaries, contributes to the problem. Metaphors can be reductive, but they can also generate a wide range of relationships between illness and the person experiencing it, as illustrated by examples including Margaret Atwood’s short story “Hairball.” Simile in particular, which expresses similarity but not equivalence and thus does not erase difference, can generate a healthy way of imagining illness. Some recent literature has suggested that doctors use metaphor to communicate with patients; this gives doctors the power to determine which metaphors will frame the illness and direct its narrative. The lessons of narrative medicine, which advocate that patients and doctors use narrative collaboratively to generate a more effective understanding and treatment of illness, need to be extended to include metaphor.
The second-look laparotomy for epithelial ovarian carcinoma
Co-authored with: L. Frigerio, L. Busci, S. Garsia, A. Ferrari.
Published in: "Italian Journal of Gynecology and Obstetrics". Vol. 2, pag. 19-24. 1990.
Summary: Between 1975 and 1986, second look laparotomy (SLL) to evaluate desease status was performed in 87 patients... more Summary: Between 1975 and 1986, second look laparotomy (SLL) to evaluate desease status was performed in 87 patients originally presenting with epithelial ovarian carcinoma. Surgical and histologic assessment did not reveal persistent desease in 34 patients (39%). The 3-years survival, by Kaplan-Meier calculation, was 73.5% after negative SLL versus 32% after posotive SLL ( p< 0.01). Residual tumor (RT) was absent after original operation in 24 patients (35.8%), in 12 cases (17.9%) RT was less than 2 cm, and in 31 cases (46.2%) RT was more than 2 cm. Negative SLL is related to RT at primary surgery. The merit of reassessment surgery is the prognostic value of this procedure: the mortality at 3 years after primary surgery was 26.5% of cases with negative SLL and 68% after positive SLL( p< 0.01).
Australian women's awareness of ovarian cancer symptoms, risk and protective factors, and estimates of own risk
by Sandra Jones
Jones SC, Magee CA, Francis J, Luxford K, Gregory P, Zorbas H & Iverson DC (2010) Australian women's awareness of ovarian cancer symptoms, risk and protective factors, and estimates of own risk. Cancer Causes and Control 21(12), 2231-2239.
OBJECTIVE: To examine Australian women's perceived risk of ovarian cancer, reasons for perceived risk levels, and... more
OBJECTIVE: To examine Australian women's perceived risk of ovarian cancer, reasons for perceived risk levels, and knowledge of ovarian cancer symptoms at two timepoints (2003 and 2007).
METHODS: A computer-assisted telephone (CATI) survey of 2,954 Australian women with no history of ovarian cancer was conducted.
RESULTS: Approximately 60% of women perceived their risk of ovarian cancer was similar to other women of their age; 10% indicated an increased risk, and 30% indicated a lower risk. These figures were similar in 2003 and 2007. Logistic regression found that lower income, increased age, being born overseas, and being retired were significantly associated with lower perceived risk (accounted for only 7.5% of the variance). Common reasons for higher perceived risk included family history of ovarian/other cancers, increasing age, and having had other types of cancer or health problems. Reasons for lower than average risk included absence of family history, having a hysterectomy, and having regular Pap smears (indicating confusion between ovarian and cervical cancer). There appeared to be substantial confusion in women's understanding of ovarian cancer symptoms; this was similar in 2003 and 2007.
CONCLUSION: The observed misperceptions and confusion regarding ovarian cancer symptoms and risk factors suggest ongoing public education campaigns are needed to improve knowledge and awareness.
Inhibition of ABCB1 (MDR1) and ABCB4 (MDR3) expression by small interfering RNA and reversal of paclitaxel resistance in human ovarian cancer cells
by K Brakora
Full text free
Ovarian cancer is currently the most lethal gynecologic malignancy in developed countries, and paclitaxel is a... more Ovarian cancer is currently the most lethal gynecologic malignancy in developed countries, and paclitaxel is a cornerstone in the treatment of this malignancy. Unfortunately, the efficacy of paclitaxel is limited by the development of drug resistance. Clinical paclitaxel resistance is often associated with ABCB1 (MDR1) overexpression, and in vitro paclitaxel resistance typically demonstrates overexpression of the ABCB1 gene. In this study, we demonstrate that paclitaxel-resistant cell lines overexpress both ABCB1 and ABCB4 (MDR3). To evaluate the role of these transporters in paclitaxel-resistant ovarian cancer cells, small interference RNAs (siRNAs) were used to target ABCB1 and ABCB4 RNA in the paclitaxel-resistant SKOV-3TR and OVCAR8TR ovarian cancer cell lines. Treatment of these lines with either chemically synthesized siRNAs or transfection with specific vectors that express targeted siRNAs demonstrated decreased mRNA and protein levels of ABCB1 or ABCB4. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays of siRNA-treated cells demonstrated 7- to 12.4-fold reduction of paclitaxel resistance in the lines treated with the synthesized siRNA of ABCB1 and 4.7- to 7.3-fold reduction of paclitaxel resistance in the cell lines transfected with siRNA of ABCB1 expressing vectors. ABCB4 siRNA-treated cell lines showed minor reduction in paclitaxel resistance. These results indicate that siRNA targeted to ABCB1 can sensitize paclitaxel-resistant ovarian cancer cells in vitro and suggest that siRNA treatment may represent a new approach for the treatment of ABCB1-mediated drug resistance.
Utility of osteopontin as a biomarker in recurrent epithelial ovarian cancer
by K Brakora
Objective. Osteopontin (OPN) is overexpressed in tumors and serum of ovarian cancer patients and may serve as a... more
Objective. Osteopontin (OPN) is overexpressed in tumors and serum of ovarian cancer patients and may serve as a biomarker. To evaluate the utility of serum osteopontin in monitoring disease status, we evaluated 234 serum samples from post-oophorectomy patients with ovarian cancer and 38 samples from healthy controls.
Methods. Serum samples were collected from 203 women with recurrent ovarian cancer and 31 newly diagnosed women participating in an experimental chemotherapeutic clinical trial. Controls included 11 young healthy women and 27 peri- or postmenopausal women without ovarian cancer. Samples were assayed for osteopontin using an enzyme-linked immunosorbent assay (ELISA) kit. Statistical analyses for group comparisons of biomarker distribution used the nonparametric Wilcoxon's rank sum test for two-group comparisons and the Kruskal–Wallis test for three-group comparisons.
Results. Osteopontin values ranged from 25 to 1463 ng/ml for patients and 25 to 617 ng/ml for controls. Mean patient levels were lower than mean control levels (74 ng/ml vs. 147 ng/ml, respectively, P = 0.0006). Serum osteopontin levels correlated with recurrent disease versus remission (68 ng/ml vs. 34 ng/ml, P = 0.0034), presence of ascites versus absence (71 ng/ml vs. 53 ng/ml, P = 0.0002), and bulky disease vs. nonbulky disease (75 ng/ml vs. 38 ng/ml, P = 0.0005). CA-125 values yielded the same trends with greater statistical difference.
Conclusions. These results demonstrate that serum osteopontin concentrations in post-oophorectomy patients with recurrent ovarian cancer are not greater than in healthy controls. Nevertheless, within this heterogeneous patient population, the values do correlate with bulk of disease. The potential utility of this assay in monitoring women with CA-125 negative disease is worthy of exploration.
Hemimethylation footprints of DNA demethylation in cancer
by Chunbo Shao
Chunbo Shao, Michelle Lacey, Louis Dubeau and Melanie Ehrlich.
Published in Epigenetics. 2009 Apr;4(3):165-75.
Hypomethylation of DNA repeats, including satellite 2 DNA (Sat2), is one of the most frequent epigenetic changes in... more
Hypomethylation of DNA repeats, including satellite 2 DNA (Sat2), is one of the most frequent epigenetic changes in cancer.
We examined ovarian epithelial tumors and diverse control tissues for methylation on only one strand (hemimethylation), both strands (symmetrical methylation), or neither strand at Sat2 CpG dyads using hairpin genomic sequencing.
Analysis of the resulting cloned DNA molecules indicated that although carcinomas displayed much symmetrical hypomethylation of CpG dyads, there was cancer-linked hypermethylation at one of the thirteen dyads in the examined 0.2-kb Sat2 region.
Hemimethylated sites were seen in both carcinomas and controls but, importantly, in carcinoma DNA molecules, they were significantly more likely to occur in clusters displaying the same orientation (the same strand methylated).
Our data suggest that hemimethylated CpG dyads are intermediates in active demethylation during carcinogenesis and not just due to a failure of maintenance methylation during replicative DNA synthesis. Constitutive heterochromatin may be especially suitable for providing a snapshot of demethylation intermediates because hemimethylation might be more long-lived in heterochromatin due to its highly condensed state.
181 views
Seen by:
A Biomarker Panel for Risk Stratification of Ovarian Tumors
by Kate Mathue
Author: Fred Ueland
Published on Touch's website
Tumor growth inhibition by olaparib in BRCA2 germline-mutated patient-derived ovarian cancer tissue xenografts.
A collaboration between KuDOS, the British Columbia Cancer Agency & Vancouver Hospital.
In press; first published online 19 Nov 2010.
Purpose:
Most patients with ovarian carcinomas succumb to their disease and there is a critical need for... more
Purpose:
Most patients with ovarian carcinomas succumb to their disease and there is a critical need for improved therapeutic approaches. Carcinomas arising in BRCA mutation carriers display defective DNA double-strand break repair that can be therapeutically exploited by inhibition of PARP-1, a key enzyme in the repair of DNA single strand breaks, creating synthetic lethality in tumour cells.
Experimental Design:
To investigate synthetic lethality in vivo, we established a BRCA2-germline-mutated xenograft model that was developed directly from human ovarian cancer tissue treated with the PARP inhibitor olaparib (AZD2281) alone and in combination with carboplatin.
Results:
We show that olaparib alone and in combination with carboplatin greatly inhibits growth in BRCA2-mutated ovarian serous carcinoma. This effect was not observed in a serous carcinoma with normal BRCA function, demonstrating a specific anti-tumor effect of olaparib in mutation carriers. Immunohistochemistry (Cleaved Caspase3 and Ki-67 stains) of remnant tissue after olaparib treatment revealed significantly decreased proliferation and increased apoptotic indices in these tumors compared to untreated controls. Furthermore, olaparib-treated tumors showed highly reduced PARP-1 activity that correlated with olaparib levels.
Conclusions:
We established a BRCA2 mutated human ovarian cancer xenograft model suitable for experimental drug testing. The demonstrated in vivo efficacy of olaparib extends on the preclinical rationale for further clinical trials targeting ovarian cancer patients with BRCA mutations.
Methodology For Mitochondrial DNA Research In Oncology: Goals And Pitfalls
Mitochondrial DNA has been described as veritable Pandora’s box of pathogenic mutations associated with a wide variety... more Mitochondrial DNA has been described as veritable Pandora’s box of pathogenic mutations associated with a wide variety of clinical syndromes including cancer. Nevertheless careful reanalysis of methodological and methodical criteria used in experiments shows that numerous papers could not be used as relevant source of clinically applicative data. It has been shown that much noise has been introduced to the interpretation of the role of mitochondrial DNA in the complex tumorigenesis process and that numerous experiments do not fulfill logical methodological criteria of case-control molecular medical experiment, as originate from technical and conceptual errors that reduce the finding of mitochondrial DNA mutations in tumors to the level of technical and methodological artifacts. Under such circumstances it remains unclear how many of the disease-associated mutations have been determined adequately and the guidelines for reanalysis of previous experiments and design of new trials are needed. This article represents and justify methodological criteria to be used in mitochondrial medicine. Proposed guidelines describe the choice of the sample and patient selection process including patient number, geographical origin and ethnicity; clinicopathological data collection with special care for additional medical factors influencing mitochondrial DNA research as mitochondria influencing diseases. Also the importance of tissue and cell extraction and normal tissue and reference sequence selection are characterized. Finally we describe three – horn dilemma and the significance of avoiding scientific silos in mitochondrial DNA research, including hypothesis formulation and verification.