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C Aquino-Parsons

Publications and source records attributed to C Aquino-Parsons.

At least 19 recordsLinked to original sources
PubMed2008

Concurrent carbogen and radiation therapy in children with high-risk brainstem gliomas.

In an attempt to improve local control, we assessed the feasibility of the addition of 4 min of carbogen inhalation (as a radiosensitizer) to daily fractionated radiotherapy in pediatric patients with high grade and/or diffuse brainstem gliomas. Ten patients inhaled carbogen for >90% of the radiation treatments. Median survival time from start of therapy was 0.80 years. Carbogen inhalation did not appear to improve the dismal prognosis.

Administration, Inhalation↗
PubMed2006

Comparison between pimonidazole binding, oxygen electrode measurements, and expression of endogenous hypoxia markers in cancer of the uterine cervix.

BACKGROUND: Although tumor hypoxia has been associated with a more aggressive phenotype and lower cure rate, there is no consensus as to the method best suited for routine measurement. Binding of the chemical hypoxia marker, pimonidazole, and expression of the endogenous hypoxia markers HIF-1alpha and CAIX were compared for their ability to detect hypoxia in tumor biopsies from 67 patients with advanced carcinoma of the cervix. METHODS: Two biopsies were taken one day after administration of pimonidazole and were analyzed for pimonidazole binding using flow cytometry or immunohistochemistry. CAIX and HIF-1alpha expression and degree of colocalization were measured in sequential antibody-stained sections. Patient subsets were examined for tumor oxygen tension using an Eppendorf electrode, S phase DNA content, or change in HIF-1alpha expression over the course of treatment. RESULTS: Approximately 6% of the tumor area stained positive for pimonidazole, HIF-1alpha, or CAIX. The CAIX positive fraction correlated with the pimonidazole positive fraction (r = 0.60). Weaker but significant correlations were observed between pimonidazole and HIF-1alpha (r = 0.31) and CAIX and HIF-1alpha (r = 0.41). Taking the extent of marker colocalization into consideration increased the confidence that all markers were identifying hypoxic regions. Over 65% of stained areas showed a high degree of colocalization with the other markers. Oxygen microelectrode measurements and S phase fraction were not correlated with the hypoxic fraction measured using the three hypoxia markers. HIF-1alpha levels tended to decrease with time after the start of therapy. CONCLUSIONS: Endogenous hypoxia marker binding shows reasonable agreement, in extent and location, with binding of pimonidazole. CAIX staining pattern is a better match to the pimonidazole staining pattern than is HIF-1alpha, and high CAIX expression in the absence (or low levels) of HIF-1alpha may indicate a different biology.

Antigens, Neoplasm↗
PubMed2005

Asynchronous burst-suppression in a child with callosal Ki-1 anaplastic large cell lymphoma.

A 13-year-old girl with Ki-1 anaplastic large cell lymphoma (Ki-1ALCL) bulky deposits in the brain developed raised intracranial pressure and coma associated with asynchronous burst-suppression following standard dose cranial irradiation. Supportive care, steroids, and chemotherapy resulted in clinical improvement. Burst-suppression coma may be reversible when secondary to tumor, decrease in steroids, or radiation effects; the asynchrony localizes the lesion to cortical interconnections such as the corpus callosum.

Adolescent↗
PubMed2005

Intratumoral oxygenation of invasive squamous cell carcimoma of the vulva is not correlated with regional lymph node metastasis.

INTRODUCTION: Tumour hypoxia has been found to be associated with tumour aggressiveness. Our primary aim was to explore the relationship between pretreatment tumour oxygenation in primary vulvar carcinoma and nodal status. Our secondary objective was to assess if there was a relationship between the clinical and biological variables. METHODS: 20 women with ISCC of the vulva were assessed with pretreatment primary tumour oxygenation with an Eppendorf pO2 probe. Patients underwent standard surgical management. Pathological assessment of the primary and nodal tissues was then performed. Primary tumour specimens were also stained for microvessel density and carbonic anhydrase IX. The relationship between smoking, preoperative Hgb, tumour CAIX expression, MVD, and Eppendorf pO2 measurements vs nodal metastasis and between these clinical and biological variables was assessed. RESULTS: Seven patients had positive lymph nodes, 13 had negative nodes. While neither current smoking status, tumour size, tumour oxygen measurements, MVD and CAIX expression correlated with metastatic nodal disease, a low preoperative Hgb correlated with pathological nodal status (p < 0.027). CONCLUSIONS: Although this analysis failed to demonstrate a strong correlation between various measures of tumour oxygenation with nodal metastasis, it may be due to the small number of patients. Only preoperative anaemia is correlated with nodal metastasis in early ISCC of the vulva.

Aged↗
PubMed2003

Small-cell carcinoma of the cervix: fourteen years of experience at a single institution using a combined-modality regimen of involved-field irradiation and platinum-based combination chemotherapy.

PURPOSE: To determine the efficacy and toxicity of a combined-modality regimen of irradiation with platinum-based combination chemotherapy in small-cell carcinoma of the cervix (SCCC). PATIENTS AND METHODS: Thirty-four patients with SCCC were seen and treated at the British Columbia Cancer Agency between May 1988 and November 2002. Two protocols were used, SMCC (May 1988 to December 1995) and SMCC2 (January 1996 to November 2002). Both protocols used cisplatin, etoposide, and involved-field irradiation (essentially pelvis plus or minus para-aortics) with concurrent chemotherapy. In addition, SMCC2 included carboplatin and paclitaxel, and the para-aortics were irradiated routinely. RESULTS: Thirty-one patients received either SMCC (n = 17) or SMCC2 (n = 14), and three patients did not (disease too extensive, n = 1; patient refusal, n = 1; and alternative regimen, n = 1). For the 31 patients treated on one of the protocols, the 3-year overall and failure-free survival (FFS) rates were 60% and 57%, respectively. The results were equivalent for SMCC and SMCC2. Radiologic stage was the only independent predictor for FFS (80% at 3 years for stage I and II patients v 38% at 3 years for stage III and IV patients). Distant failure (28%) was the most common cause of failure, with local failure occurring in 13% of patients. The switch to SMCC2 did not improve efficacy but did lessen the toxicity. CONCLUSION: SCCC can be successfully treated in approximately 55% of patients with a combination of irradiation and platinum-based chemotherapy. Disease extent predicts for chance of curability.

Adult↗
PubMed2003

The effect of deep inspiration breath-hold on tumour oxygenation.

AIM: To investigate the influence of deep inspiration breath-hold on the oxygen tension of in-vivo tumours measured using an Eppendorf pO2 histograph. MATERIALS AND METHODS: Patients with accessible primary or metastatic tumours > or = 2 cm diameter were entered into a protocol measuring tumour oxygenation with an Eppendorf pO2 histograph during normal breathing (NB) and deep inspiration breath-hold (DIBH). Change in oxygen tension was assessed using the Wilcoxon Signed Ranks test. RESULTS: Thirty patients were entered in to this protocol. The median maximum tumour dimension was 4 cm. The median of the median pO2 of these tumours was 18 mmHg. Tumours were assessed during NB and DIBH. Oxygen tension measurements along 1-3 pairs of tracks per tumour (median of 2) were obtained. The median number of measurements per track was 30 for NB and 29 for DIBH (range 17-59). In six tumours, the values during NB were significantly higher than during DIBH, whereas, for six other tumours, the relationship was the opposite; for the remaining 18 patients, no significant difference was observed. CONCLUSION: These data show heterogeneity of tumour oxygenation seen with in-situ tumours both at baseline and as a result of DIBH. No systematic change in the Eppendorf pO2 measurements was seen as a result of DIBH; however, the individual tumour responses to DIBH varied dramatically.

Adult↗
PubMed2001

Carbonic anhydrase 9 as an endogenous marker for hypoxic cells in cervical cancer.

The presence of radiation-resistant hypoxic cells in some solid tumors is known to predict for relapse after radiotherapy. Use of an endogenous marker of hypoxia would be a convenient alternative to current methods that measure tumor oxygenation, provided the marker could be shown to reliably identify viable, radiation-resistant, hypoxic cells. Carbonic anhydrase 9 (CA9) is a transmembrane protein overexpressed in a wide variety of tumor types and induced by hypoxia. Using a monoclonal antibody and cell sorting, CA9-positive cells in SiHa cervical carcinoma xenografts growing in immunodeficient mice were found to be clonogenic, resistant to killing by ionizing radiation, and preferentially able to bind the hypoxia marker pimonidazole. CA9 and pimonidazole immunostaining were compared in formalin-fixed sections from tumors of 18 patients undergoing treatment for cancer of the cervix. Excellent colocalization was observed, although the area of the tumor section that bound anti-CA9 antibodies represented double the number of cells that bound anti-pimonidazole antibodies. Occasional regions staining with pimonidazole but not CA9 could be indicative of transient changes in tumor perfusion. Results support the hypothesis that CA9 is a useful endogenous marker of tumor hypoxia.

Animals↗
PubMed2001

Early stage uterine papillary serous carcinoma of the endometrium: effect of adjuvant whole abdominal radiotherapy and pathologic parameters on outcome.

BACKGROUND: Uterine papillary serous carcinoma (UPSC) is an aggressive subtype of endometrial cancer, behaving like ovarian epithelial cancers and having a predilection for transperitoneal relapse. Within this subtype of uterine cancers, predictors of outcome and the role of adjuvant therapies have not been firmly established, to the authors' knowledge. METHODS: Between 1985-1995, 78 patients who had International Federation of Gynecology and Obstetrics (FIGO) Stage I, II, or IIIa UPSC (based on positive washings only) were seen at the British Columbia Cancer Agency. During this time, the authors had a policy of offering adjuvant pelvic, paraaortic and whole-abdominal radiotherapy (WART) to these patients. Fifty-eight patients received adjuvant WART, and 20 received lesser or no adjuvant therapy. The authors undertook a retrospective analysis of pathology with quantification of the percentage of papillary serous component (% PSC) and p53 expression. Pathology was retrieved and reviewed on 62 patients; p53 staining was performed on blocks from the hysterectomy specimen in 46 cases. Pathologic parameters, stage, and adjuvant therapy were correlated with clinical outcome in a multivariate analysis. RESULTS: Median follow-up was 52 months (3-139 mos) and the 5-year disease-specific survival rate was 66.2%. The 58 patients who received adjuvant WART had a significantly better 5-year disease-specific survival than those 20 patients who did not, 74.9% versus 41.3% (P = 0.04). Multivariate analysis showed that % PSC and p53 were not significant predictors of outcome for early stage UPSC. Of the factors examined, only FIGO stage and WART significantly predicted improved outcome (P = 0.02 and 0.04, respectively). CONCLUSIONS: The current study demonstrated a significant difference in the outcomes of patients who had FIGO Stage I compared with Stage II UPSC. In the current series of patients, the authors were not able to predict outcome based on % PSC or p53 expression. The current study results with WART were promising, and WART merits further study.

Adult↗
PubMed2001

A pilot study comparing intratumoral oxygenation using the comet assay following 2.5% and 5% carbogen and 100% oxygen.

PURPOSE: Tumor hypoxia has been purported to be an important biologic factor in the failure of radical radiotherapy to achieve local control in many tumor types. This study was designed to evaluate the effect of breathing high oxygen content gas mixtures (oxygen with 0%, 2.5%, or 5% carbon dioxide) on tumor oxygenation measured using the Eppendorf polarographic oxygen electrode and the comet assay in accessible, hypoxic human tumors. METHODS AND MATERIALS: Using Eppendorf pO2 histography to identify hypoxic tumors (median pO2 < or = 10 mmHg), eligible patients were systematically allocated either 100% oxygen (O2) or oxygen with 2.5% or 5% carbon dioxide (CO2). Tumors were treated with 6-10 Gy during which two fine needle aspirates (FNA) were obtained from different regions of the lesion, one at midway and the other at completion of the radiation exposure. Gas breathing was initiated 4 min before radiation was commenced. A 10-min interval was specified between the first and second halves of the radiation exposure to allow near maximal DNA repair prior to the second half of the radiation treatment. FNAs were performed within 2 min of cessation of radiation and the cells immediately suspended in buffered saline at 4 degrees C for analyses of hypoxic fraction using the comet assay. RESULTS: Fifteen evaluations were performed in 13 patients with hypoxic tumors (median O2 tension 2.75 mmHg) treated with a median dose of 8 Gy. The median hypoxic fraction determined using the comet assay fell from 0.36 to 0.13 (p = 0.001, Wilcoxon signed rank test) due to the addition of high oxygen content gases. CONCLUSIONS: In tumors defined as hypoxic using Eppendorf pO2 histography, a statistically significant reduction in the hypoxic fraction with the comet assay was found following administration of high oxygen content gases. These preliminary findings reveal a trend suggesting that 5% carbogen may reduce the hypoxic fraction by a greater margin than either 100% oxygen or 2.5% carbogen.

Analysis of Variance↗
PubMed2001

Non-constant tumour blood flow--implications for therapy.

In the past few years, 'perfusion-limited' hypoxia caused by intermittent decreases in tumour blood flow has received increasing attention. Little effort, however, has gone into characterizing the nature, magnitude or duration of these changes, or their functional significance other than as modifiers of radiotherapy. We have therefore undertaken multiple, quantitative analyses of tumour blood flow in human tumour xenograft systems, and rigorously examined the ramifications of transient blood flow changes. Tumour blood flow in these experimental tumours is much less constant than has previously been assumed, and not only impacts on response to radiotherapy and chemotherapy, but also on the more fundamental processes of tumour growth and repopulation. Notably, responses entirely consistent with the laboratory results have been seen in our initial studies of human tumours sequentially biopsied during treatment.

Adenocarcinoma↗
PubMed2001

Measuring hypoxia in solid tumours--is there a gold standard?

Tumour hypoxia is known to be associated with aggressiveness and poor response to treatment, which has stimulated the development of several methods able to detect hypoxic tumours. To date, only one method, the oxygen microelectrode, has been used to provide pretreatment measures of tumour oxygenation that correlate with local control and disease-free survival. In an effort to validate new methods, comparisons have been made between the Eppendorf oxygen microelectrode, the comet assay, and hypoxia marker binding in tumours of patients undergoing curative treatment or palliative radiotherapy. These comparisons suggest that tumours with median oxygen tensions below 10 mmHg have relatively high hypoxic fractions as measured by the comet assay (> 0.20). The fraction of cells that binds pimonidazole, detected in cells obtained by fine-needle aspiration biopsy, correlates well with the hypoxic fraction measured using the comet assay. However, in general, hypoxic fractions measured by the comet assay and pimonidazole binding correlate only poorly with Eppendorf measurements performed for the same tumour. Factors that might be responsible for these differences, and problems associated with measuring the 'relevant' hypoxic population are discussed.

Biopsy, Needle↗
PubMed2001

Clinical relevance of intermittent tumour blood flow.

One of the goals of translational cancer research is to understand basic 'phenomena' so that tumour response to therapy can be improved. One such phenomenon is intermittent tumour blood flow. The impact of the transient hypoxia that results from decreased tumour blood flow is now beginning to be appreciated in preclinical systems, and also receiving some attention in clinical practise. Thus in this article we review the nature and frequency of microregional blood flow changes in preclinical and clinical tumours and examine the impact of those changes on response to both radiotherapy and chemotherapy. Additionally, the implications of non-constant blood flow for both the growth of the unperturbed tumour and the regrowth of surviving tumour clonogens during and after therapy are examined.

Antineoplastic Agents↗
PubMed2000

Oxygen tension in primary gynaecological tumours: the influence of carbon dioxide concentration.

BACKGROUND AND PURPOSE: To assess the effect of inhalation of various high oxygen content gases (HOCG) with different carbon dioxide concentrations on the tumour oxygen tension in patients with primary gynaecological malignancies. MATERIALS AND METHODS: Tumour oxygen tension was assessed on two protocols in those patients with locally advanced visible or palpable primary gynaecological malignancies. Patients were assessed initially while breathing room air (R/A). After 4 min of inhaling the first HOCG, a second assessment of the oxygen tension within the tumour was made. After a 10 min rest period while inhaling R/A, the second HOCG was administered for 4 min after which the third set of measurements were obtained. Protocol A involved assessing the tumour oxygen tension in 12 patients while breathing R/A, 100% oxygen (O(2)) and 5% carbogen (95% O(2), 5% CO(2)). For protocol B, tumour oxygen tension assessments of 13 patients while breathing R/A, 2.5% carbogen (97.5% O(2), 2.5% CO(2)), and 5% carbogen. Median pO(2) and percentage of values </=2.5 mmHg were assessed. RESULTS: Regarding protocol A, the median of the median pO(2) values increased from 5 mmHg when breathing R/A to 47 mmHg for 100% O(2) and to 105 mmHg for 5% carbogen inhalation. The median of the percentage of values </=2. 5 mmHg decreased: 17% for R/A vs. 16% for 100% O(2) (P=ns) vs. 0% for 5% carbogen (P=0.015). In protocol B, the median of the median pO(2) values increased from 3 mmHg when breathing R/A to 73 mmHg when inhaling 2.5% carbogen and to 72 mmHg for 5% carbogen inhalation. The median of the percentage of values </=2.5 mmHg decreased with both carbogen mixtures compared with room air: 42% for R/A vs. 0% for 2.5% carbogen (P=0.05) and 3% for 5% carbogen (P=0.015). No statistically significant difference in this parameter was found between the two carbogen concentrations. CONCLUSION: Oxygen tension as measured with an Eppendorf pO(2) histograph, increased with inhalation of the oxygen and carbon dioxide gas mixtures tested. While 100% oxygen inhalation increased the median pO(2) compared with R/A a significantly greater increase in oxygen tension was seen with inhalation of either carbogen gas mixture. Pure oxygen inhalation did not decrease the percentage of values </=2.5 mmHg whereas inhalation of either 2.5 and 5% carbogen gas resulted in a significant decrease in this parameter. Both carbogen concentrations appear equal at increasing the oxygen tension in primary gynaecological tumours as measured with the Eppendorf pO(2) histograph.

Administration, Inhalation↗
PubMed2000

Comparison between the comet assay and pimonidazole binding for measuring tumour hypoxia.

Pimonidazole is finding increasing use in histochemical analyses of hypoxia in tumours. Whether it can identify every hypoxic cell in a tumour, and whether the usual subjective criteria used to define 'positive' cells are optimal, are less certain. Therefore, our aim was to develop an objective flow cytometry procedure for quantifying pimonidazole binding in tumours, and to validate this method by using a more direct indicator of radiobiologic hypoxia, the comet assay. SCCVII tumours in C3H mice were analysed for pimonidazole binding using flow cytometry and an iterative curve-fitting procedure, and the results were compared to the comet assay for the same cell suspensions. On average, cells defined as anoxic by flow analysis (n = 43 tumours) bound 10.8 +/- 0.95 times more antibody than aerobic cells. In samples containing known mixtures of aerobic and anoxic cells, hypoxic fractions as low as 0.5% could easily be detected. To assess the flow cytometry assay under a wider range of tumour oxygen contents, mice were injected with hydralazine to reduce tumour blood flow, or allowed to breathe various gas mixtures during the 90 min exposure to pimonidazole. Hypoxic fraction estimated by the pimonidazole binding method agreed well with the hypoxic fraction measured using the comet assay in SCCVII tumours (r2 = 0.87, slope = 0.98), with similar results in human U87 glioma cells and SiHa cervical carcinoma xenografts. We therefore conclude that this objective analysis of pimonidazole labelling by flow cytometry gives a convenient and accurate estimate of radiobiological hypoxia. Preliminary analyses of biopsies from 3 patients given 0.5 g m-2 pimonidazole also suggest the suitability of this approach for human tumours.

Animals↗
PubMed1999

Carbogen inhalation in cervical cancer: assessment of oxygenation change.

OBJECTIVE: Our objectives were (1) to examine tumor oxygenation measured with an Eppendorf pO(2) histograph, prior to and during carbogen (95% oxygen, 5% carbon dioxide) breathing in patients with primary cervical cancer; and (2) to assess the feasibility of delivering external beam radiation therapy and concurrent carbogen to patients treated for cervical cancer. METHODS: Pretreatment tumoral pO(2) measurements were obtained using an Eppendorf pO(2) histograph in patients with primary cervical cancers while breathing room air and after 4 min of carbogen breathing. Patients able to tolerate the carbogen inhalation were asked to inhale it for 4 min prior to and during all external beam radiation therapy. RESULTS: Two sets of pO(2) measurements were obtained from 25 patients. The average median pO(2) increased from 8 mm Hg when breathing room air to 96 mm Hg after carbogen breathing. Twenty-four of 25 patients tolerated the carbogen; they inhaled carbogen during their daily external beam radiation therapy. All 24 patients completed their planned course of external beam radiation therapy and daily concurrent carbogen without significant difficulty. CONCLUSION: (1) Carbogen inhalation increased the average median pO(2) value 10-fold and decreased the percentage of values </=2.5 and 5 mm Hg. (2) Carbogen inhalation is feasible during external beam pelvic radiation.

Administration, Inhalation↗
PubMed1999

Comparison between the comet assay and the oxygen microelectrode for measurement of tumor hypoxia.

BACKGROUND AND PURPOSE: Hypoxic cells are present in some solid tumours and are known to limit radiocurability. To compare two measures of tumour hypoxia, 25 patients with locally advanced disease and accessible tumours or metastatic nodes were examined using an oxygen microelectrode and the alkaline comet assay. MEASUREMENTS AND METHODS: For the comet assay, fine needle aspirate biopsies were taken immediately following a dose of 5-10 Gy. Single cells were examined for radiation-induced DNA strand breaks, and the percentage of radio-resistant hypoxic cells within the population was calculated from DNA damage histograms. For oxygen tension (pO2) measurements, multiple tracks were made using an Eppendorf oxygen microelectrode. The possibility that application of the first method might influence hypoxic fraction measurement by the second method was examined in a more controlled system by creating four tracks in murine SCC-VII tumours using an oxygen electrode, and measuring hypoxic fraction at subsequent times. RESULTS: For 28 tumours from 25 patients, hypoxic fraction measured by comet assay correlated with the percentage of PO2 values < 5 mmHg (r2 = 0.46, P < 0.001). The mean comet hypoxic fraction was 0.36 for five tumours with a median PO2 < 10 mmHg. For the remaining 23 tumours with a median PO2 > 10 mmHg, the mean hypoxic fraction was 0.09. Advancement of an oxygen electrode through SCCVII tumours had no significant effect on hypoxic fraction measured 5 min to 24 h later using the alkaline comet assay. CONCLUSIONS: Tumours defined as hypoxic based on a median pO2 < 10 mmHg appear to contain more than 20% radio-biologically hypoxic cells as estimated by the comet assay. In an animal tumour model, puncture of the tumour with an oxygen electrode did not influence hypoxic fraction measured using the comet assay, in agreement with the clinical data that the order in which the two methods were performed was not important.

Animals↗
PubMed1999

The comet assay in clinical practice.

The comet assay is a single-cell gel electrophoresis technique that measures DNA damage in individual cells. Since radiation produces 3-4 times more DNA damage in well-oxygenated cells compared with hypoxic cells, this assay can quantify the fraction of radiation-resistant hypoxic cells found in many solid tumours. This paper summarizes our results with 73 accessible metastatic tumours irradiated with palliative intent. Hypoxic fractions ranged from 0.0 to 0.67 with a mean of 0.15; 62% of these advanced tumours showed a hypoxic fraction > 0.05. Comparisons between two sequential aspirates in 33 tumours gave a slope of 0.92 (r2 = 0.88), suggesting that a single aspirate is generally representative of the tumour. A limitation, however, is that the hypoxic fraction could not be measured in clinical samples given a conventional dose of 2 Gy.

Animals↗