Practical considerations for collecting confocal images.
Explore the source record for details and available documents.
Diagnostic Imaging↗
Biomedical subjects
D Carter
Publications and source records attributed to D Carter.
Premenstrual symptoms in women with premenstrual asthma.
STUDY OBJECTIVES: To characterize and compare premenstrual symptoms (mood, physical) throughout two menstrual cycles with and without estradiol administration, in women with premenstrual asthma (PMA), and to examine relationships between asthma symptoms versus premenstrual symptoms and pulmonary function versus premenstrual symptoms in these women. DESIGN: Open-label, longitudinal, 9-week study (consisting of two complete menstrual cycles). SETTING: Clinical study at the University of Kentucky; data analysis at the University of British Columbia and Children's and Women's Health Centre of British Columbia. PATIENTS: Fourteen women (age 35.6 +/- 6.6 yrs) with mild to moderate asthma with a baseline ratio of forced expiratory volume in 1 second:forced vital capacity of 0.72 +/- 0.12. INTERVENTIONS: Women were followed for two complete menstrual cycles. During the second complete cycle (i.e., cycle 3), they received estradiol 2 mg orally between days 23 and 28 (premenstrual). MEASUREMENTS AND MAIN RESULTS: Throughout both cycles 2 and 3, each subject recorded premenstrual symptom questionnaire scores (15 mood and physical symptoms, graded 0-3) every morning on awakening. Peak expiratory flow rate (PEFR) and visual analog scales of asthma symptoms (cough, wheezing, breathlessness, chest tightness) were recorded daily at the same time. Seven subjects showed a classic pattern of premenstrual symptoms. Four of the five subjects who complained of PMA symptoms at study enrollment also demonstrated this classic pattern of premenstrual symptoms. After estradiol administration, four women had lower symptom scores, eight had higher scores, and two had the same scores. Overall, estradiol had no significant effect on symptoms (mean area under the curve 18.9 +/- 14.8 day(-1) vs 20.3 +/- 14.8 day(-1), p>0.05). Ten subjects had significant relationships between asthma symptoms and premenstrual symptoms, whereas six had significant relationships between PEFR and premenstrual symptoms. CONCLUSIONS: Exogenous estradiol administration had no significant effect on premenstrual symptoms in women with PMA. The lack of a significant effect allows for patient blinding in a placebo-controlled, crossover study of exogenous estradiol in PMA that is currently under way Clinical implications of relationships between asthma symptoms versus premenstrual symptoms and pulmonary function versus premenstrual symptoms may warrant further study.
Adult↗
Biomechanical evaluation of fixation of intra-articular fractures of the distal part of the radius in cadavera: Kirschner wires compared with calcium-phosphate bone cement.
BACKGROUND: The purpose of this study was to compare the biomechanical efficacy of an injectable calcium-phosphate bone cement (Skeletal Repair System [SRS]) with that of Kirschner wires for the fixation of intraarticular fractures of the distal part of the radius. METHODS: Colles fractures (AO pattern, C2.1) were produced in ten pairs of fresh-frozen human cadaveric radii. One radius from each pair was randomly chosen for stabilization with SRS bone cement. These ten radii were treated with open incision, impaction of loose cancellous bone with use of a Freer elevator, and placement of the SRS bone cement by injection. In the ten control specimens, the fracture was stabilized with use of two horizontal and two oblique Kirschner wires. The specimens were cyclically loaded to a peak load of 200 newtons for 2000 cycles to evaluate the amount of settling, or radial shortening, under conditions simulating postoperative loading with the limb in a cast. Each specimen then was loaded to failure to determine its ultimate strength. RESULTS: The amount of radial shortening was highly variable among the specimens, but it was consistently higher in the Kirschner-wire constructs than in the bone fixed with SRS bone cement within each pair of radii. The range of shortening for all twenty specimens was 0.18 to 4.51 millimeters. The average amount of shortening in the SRS constructs was 50 percent of that in the Kirschner-wire constructs (0.51+/-0.34 compared with 1.01+/-1.23 millimeters; p = 0.015). With the numbers available, no significant difference in ultimate strength was detected between the two fixation groups. CONCLUSIONS: This study showed that fixation of an intra-articular fracture of the distal part of a cadaveric radius with biocompatible calcium-phosphate bone cement produced results that were biomechanically comparable with those produced by fixation with Kirschner wires. However, the constructs that were fixed with calcium-phosphate bone cement demonstrated less shortening under simulated cyclic load-bearing.
Biomechanical Phenomena↗
Comparison of rebiopsy rates after stereotactic core needle biopsy of the breast with 11-gauge vacuum suction probe versus 14-gauge needle and automatic gun.
OBJECTIVE: The 11-gauge vacuum suction probe is an alternative to the 14-gauge needle and automatic gun for performing stereotactic core needle biopsies. This study compares rebiopsy rates after stereotactic core needle biopsies that were performed with the two methods. The study also assesses the outcomes of those repeat biopsies. MATERIALS AND METHODS: Five hundred ninety-two stereotactic core needle biopsies using a 14-gauge needle and automatic gun and 354 using an 11-gauge vacuum suction probe were performed consecutively. Excluding malignancies, the number of cases requiring rebiopsy and the reasons for rebiopsy were determined for each group. The histologic diagnoses of the repeat biopsies were assessed. RESULTS: The rebiopsy rate was significantly lower with the 11-gauge vacuum suction probe (9.0%) than with the 14-gauge needle and automatic gun (14.9%) (p = .013). Significant reductions were found in cases of insufficient sampling (probe, 1.7%; needle, 4.4%; p = .042) and mammographic-pathologic discrepancy (probe, 0.8%; needle, 3.4%; p = .026). The rebiopsy rate for masses was 6.1% with the vacuum probe versus 10.7% with the 14-gauge needle (p = .12) and for calcifications was 11.6% with the vacuum probe versus 23.7% with the 14-gauge needle (p = .003). After rebiopsy, the percentage of cases in which malignancy was found was 18.5% with the vacuum probe versus 13.7% with the 14-gauge needle. On rebiopsy, the percentage of malignancies found in each category were atypical hyperplasia: probe 26.7%, needle 20.0%; insufficient sample: probe 0%, needle 9.5%; pathologist recommendation: probe 50.0%, needle 12.5%; and lobular carcinoma in situ: probe 0%, needle 100%. CONCLUSION: Use of the 11-gauge vacuum-assisted device significantly decreases but does not eliminate the need for rebiopsy after stereotactic core needle biopsy. The rebiopsy rate for calcifications was significantly reduced by using the vacuum suction probe rather than the 14-gauge needle; however, the rate for masses was reduced only slightly. On rebiopsy, malignancies were found in both groups.
Biopsy, Needle↗
Identification of different gene expression patterns in low and high grade non-Hodgkin's lymphomas by differential display.
We have compared the patterns of gene expression in non-Hodgkin's lymphoma (NHL) biopsy samples from patients with either low grade or high grade disease, by the polymerase chain reaction (PCR) based technique of differential display. By using a combination of 30 primer pairs we estimate that we were able to survey over 3,000 genes expressed in these tissues. In this study we compared a group of three low grade follicular centre lymphomas with a group of two high grade diffuse large cell lymphomas and scored only those PCR products that were represented in all samples of each group. In doing so we were able to avoid many of the problems associated with the occurence of false PCR-positives. 139 differences were then scored as representing genes which may be differentially expressed during the transformation from low to high grade disease. However, as many of these might simply reflect changing populations of cells, we focused on only those genes which appeared to be expressed exclusively in either low grade or high grade disease. We have identified 14 such genes, of which 10 were low grade specific and 4 were high grade specific. This approach therefore appears to offer a systematic method for the identification and characterisation of differentially expressed genes, which are characteristic of different NHL sub-types.
Base Sequence↗
Environmental exposure to hexachlorobenzene (HCB) and risk of female breast cancer in Connecticut.
Earlier studies have provided inconclusive results relating hexachlorobenzene (HCB), an organochlorine fungicide, to female breast cancer risk. The current study, with a total of 304 breast cancer cases and 186 controls recruited in Connecticut between 1994 and 1997, examined the association by directly comparing breast adipose tissue levels of HCB between incident breast cancer cases and noncancer controls. The cases and controls were patients who had breast biopsies or surgery at the Yale-New Haven Hospital (New Haven, CT) and histologically diagnosed either as breast cancer or benign breast disease. Information on major known or suspected risk factors for breast cancer was obtained through in-person interview by trained interviewers. No significant difference in mean breast adipose tissue levels of HCB was observed between breast cancer patients (21.0 ppb) and controls (19.1 ppb) in this large case-control study. The risk also did not vary significantly by menopausal status, estrogen or progesterone receptor status of the breast cancer cases, breast cancer histology, stage of diagnosis, or type of benign breast disease. Among parous women who reported ever breast feeding, an odds ratio (OR) of 0.5 [95% confidence interval (CI), 0.2-1.4] was observed when the highest quartile was compared with the lowest quartile. However, no association was observed among parous women who reported never breast feeding (OR = 0.7; 95% CI, 0.3-1.7 for the fourth quartile). For nulliparous women, the adjusted OR was 2.1 (95% CI, 0.5-8.8) for the third tertile when compared with the lowest based on few subjects. Therefore, our study does not support a positive association between environmental exposure to HCB and risk of breast cancer.
Adipose Tissue↗
Transcutaneous carbon dioxide threshold during exercise.
BACKGROUND: To study the possible use of transcutaneous carbon dioxide pressure measurements to estimate ventilatory threshold during exercise. METHODS EXPERIMENTAL DESIGN: comparative study. SETTINGS: Institutional practice, ambulatory care. Patients and measures: seventy-nine subjects. INTERVENTION: incremental exercise tests with simultaneous recordings of breath by breath gas exchange and transcutaneous carbon dioxide pressure. MEASURES: Six reviewers determined the ventilatory threshold using both the graphs for the carbon dioxide excretion to oxygen consumption relationship: V slope technique (VTa), and the ventilatory equivalent for oxygen uptake changes over time: (VTb), the respiratory compensation point (RCP) on ventilatory equivalent for carbon dioxide, and the transcutaneous threshold (Ttc) on the transcutaneous carbon dioxide pressure changes over time respectively. RESULTS: A Ttc could be defined by all observers in 85% of the subjects. Correlation between Ttc and VT expressed as oxygen consumption absolute values ranged from 0.971 to 0.975 on the mean values of six observers. Using the Bland-Altmann approach, differences (mean +/- SD) were 13 +/- 215, -40 +/- 204, 231 +/- 221 ml.min-1 between Ttc and VTa, RCP respectively. A difference of 38 +/- 173 ml.min-1 was found between VTa and VTb. This suggests that Ttc shows little difference with VT but not with RCP. CONCLUSIONS: We suggest that a carbon dioxide transcutaneous threshold can be found close to the ventilatory threshold. Potential clinical use of transcutaneous device are vast.
Adolescent↗
Breast carcinoma tumor characteristics in black and white women.
BACKGROUND: A significant disparity in mortality rates exists between black and white patients with breast carcinoma. This study was designed to compare breast carcinoma tumor characteristics by race and to examine the possible reasons for these differences. METHODS: Female patients with an initial diagnosis of breast carcinoma between January 1, 1985 and December 31, 1993 were selected from the Yale-New Haven Hospital Tumor Registry for this retrospective cohort study. All black patients were eligible and white patients were selected randomly and matched to each black patient by year of diagnosis. Data were gathered from multiple sources including the hospital, the Connecticut Tumor Registry, and the U. S. Census. All pathology specimens were reviewed at Yale-New Haven Hospital. RESULTS: The final cohort had 100 black and 300 white patients. The black patients tended to be younger than white patients at the time of diagnosis (mean age 55 years vs. 60 years; P = 0.001). A significant racial difference was noted in eight tumor characteristics: stage, size of the tumor, lymph node status, presence of necrosis, vascular/lymphatic invasion, ductal carcinoma in situ, perineural invasion, and progesterone receptor status. Although income, medical insurance coverage, and method of tumor detection explained some pathology differences, black patients still were more likely to have necrosis and a larger tumor size, even after adjustment. CONCLUSIONS: Black patients with breast carcinoma tend to be diagnosed at a younger age and in a few important respects have different tumor characteristics compared with white patients, even after controlling for income, medical insurance coverage, and method of tumor detection after screening mammography. These differences may have etiologic and clinical implications.
Adult↗
Expression of AP-2 transcription factors in human breast cancer correlates with the regulation of multiple growth factor signalling pathways.
The AP-2 transcription factors are required for normal growth and morphogenesis during mammalian development. Previous in vitro studies have also indicated that the AP-2 family of proteins may be involved in the etiology of human breast cancer. The AP-2 genes are expressed in many human breast cancer cell lines, and critical AP-2-binding sites are present in both the ERBB-2 (HER2/neu) and estrogen receptor promoters. We have now characterized immunological reagents that enable specific AP-2 family members, including AP-2alpha and AP-2gamma, to be detected in human breast cancer epithelium. Data obtained with these reagents demonstrate that whereas AP-2alpha and AP-2gamma are both present in benign breast epithelia, there is a significant up-regulation of AP-2gamma expression in breast cancer specimens (P = 0.01). There was also a significant correlation between the presence of the AP-2alpha protein and estrogen receptor expression (P = 0.018) and between specimens containing both AP-2alpha/AP-2gamma proteins and ERBB-2 expression (P = 0.003). Furthermore, we detected an association (P = 0.04) between the expression of AP-2gamma and the presence of an additional signal transduction molecule implicated in breast cancer, the insulin-like growth factor I receptor. Analysis of the proximal promoter of the insulin-like growth factor I receptor revealed a novel AP-2-binding site. Thus, AP-2 proteins may directly regulate the transcription of this growth factor receptor. Taken together, these data strongly support a role for the AP-2 gene family in the control of cell growth and differentiation in breast cancer.
Binding Sites↗
Transforming growth factor beta type I receptor kinase mutant associated with metastatic breast cancer.
Malignant breast carcinoma cell lines are frequently refractory to transforming growth factor beta (TGF-beta)-mediated cell cycle arrest. To identify molecular mechanisms of TGF-beta resistance, we have conducted a comprehensive structural analysis of the TGF-beta receptor types I (TbetaR-I) and II (TbetaR-II) genes in primary human breast carcinomas and associated axillary lymph node metastases. No evidence for loss of expression (n=14) or structural alterations of the TbetaR-II gene (n=30) were identified. However, 2 of 31 primary carcinomas and 5 of 12 lymph node metastases carried a C to A transversion mutation resulting in a serine to tyrosine substitution at codon 387 (S387Y) of the TbetaR-I receptor gene. This TbetaR-I mutant has a diminished ability to mediate TGF-beta-dependent effects on gene expression as compared with wild-type TbetaR-I. S387Y is the first reported mutation in the TbetaR-I gene in human cancer that was primarily associated with lymph node metastases in the present series.
Amino Acid Sequence↗
Crystal structures of Toxoplasma gondii uracil phosphoribosyltransferase reveal the atomic basis of pyrimidine discrimination and prodrug binding.
Uracil phosphoribosyltransferase (UPRTase) catalyzes the transfer of a ribosyl phosphate group from alpha-D-5-phosphoribosyl-1-pyrophosphate to the N1 nitrogen of uracil. The UPRTase from the opportunistic pathogen Toxoplasma gondii is a rational target for antiparasitic drug design. To aid in structure-based drug design studies against toxoplasmosis, the crystal structures of the T.gondii apo UPRTase (1.93 A resolution), the UPRTase bound to its substrate, uracil (2.2 A resolution), its product, UMP (2.5 A resolution), and the prodrug, 5-fluorouracil (2.3 A resolution), have been determined. These structures reveal that UPRTase recognizes uracil through polypeptide backbone hydrogen bonds to the uracil exocyclic O2 and endocyclic N3 atoms and a backbone-water-exocyclic O4 oxygen hydrogen bond. This stereochemical arrangement and the architecture of the uracil-binding pocket reveal why cytosine and pyrimidines with exocyclic substituents at ring position 5 larger than fluorine, including thymine, cannot bind to the enzyme. Strikingly, the T. gondii UPRTase contains a 22 residue insertion within the conserved PRTase fold that forms an extended antiparallel beta-arm. Leu92, at the tip of this arm, functions to cap the active site of its dimer mate, thereby inhibiting the escape of the substrate-binding water molecule.
Amino Acid Sequence↗
Localization and targeting of the Leishmania donovani hypoxanthine-guanine phosphoribosyltransferase to the glycosome.
Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) is a key enzyme in the purine salvage pathway of many protozoan parasites. The predicted amino acid sequences of certain HGPRT proteins from parasites of the Trypanosomatidae family reveal a COOH-terminal tripeptide signal that is consistent with the degenerate topogenic signal targeting proteins to the glycosome, a fuel-metabolizing microbody unique to these parasites. To determine definitively the intracellular milieu of HGPRT in these pathogens, polyclonal antiserum to the purified recombinant HGPRT from Leishmania donovani was generated in rabbits, and confocal and immunoelectron microscopy were employed to establish that the L. donovani HGPRT is localized exclusively to the glycosome. No HGPRT protein was detected in delta hgprt null mutants in which both alleles of the HGPRT locus had been replaced by a drug-resistance cassette. Transfectants of the delta hgprt knockout strain in which a wildtype HGPRT was amplified on an expression plasmid contained augmented amounts of HGPRT, all of which was localized to the glycosome. delta hgprt transfectants containing amplified copies of a mutated HGPRT construct in which the Ser-Lys-Val COOH-terminal targeting signal had been deleted expressed HGPRT throughout the parasite, including subcellular organelles such as the nucleus and flagellum. These data demonstrate that the L. donovani HGPRT is compartmentalized exclusively within the glycosome and that the COOH-terminal tripeptide of the protein is necessary to achieve targeting to this organelle.
Animals↗
Breast carcinoma associated with necrotic granulomas in axillary lymph nodes.
From a series of 100 consecutive breast carcinomas with axillary lymph node metastases, two cases of necrotic granulomas in the nodes are presented. Lymph nodes in each case were characterized by areas of necrosis surrounded by a palisade of cells resembling histiocytes as seen in a rheumatoid nodule. Although the initial impression was that of a reactive granuloma, when immunostained for keratin and EMA, the areas of necrosis showed positive staining for keratin and EMA in a cytoplasmic pattern. The surrounding palisade of cells stained with histiocyte markers, while the necrotic area itself was negative. Staining for both estrogen and progesterone markers was also negative. Staining of nine lymph nodes with caseating granulomas not associated with carcinoma with the same panel of antibodies revealed no staining except for irregular, noncellular staining with EMA. This pattern of necrosis in axillary lymph nodes from two cases of breast carcinoma was interpreted as evidence of necrotic metastatic tumor cells. Necrosis in axillary lymph nodes associated with invasive breast cancer should arouse suspicion for metastasis.
Axilla↗
Sudden death due to undetected mediastinal germ cell tumor.
A 32-year old man, apparently asymptomatic, was found dead in his apartment. Autopsy revealed a large necrotic mediastinal mass with liver and occipital brain metastases, the latter having produced acute intraparenchymal and intraventricular hemorrhage with cerebellar tonsillar herniation. Histologically, the mediastinal mass and metastases were consistent with immature extragonadal teratoma, with malignant transformation of the intestinal-type epithelium. Undiagnosed neoplasms as causes of sudden death are quite rare and usually reported in older age groups; however, in one study of autopsies in a 25-to 46-year-old age group, a significant 3.2% was reported. Germ cell tumors of the mediastinum are the most common extragonadal primary site, accounting for approximately 50%-70% of extragonadal germ cell tumors (EGCTs) and primarily affecting 20- to 35-year-old men. EGCTs are usually symptomatic at the time of diagnosis, although a large proportion may be asymptomatic. This case represents one the few reported cases of sudden death as a result of mediastinal EGCT; it also demonstrates the natural course of this disease and underscores the importance of medicolegal autopsies in cases of sudden death.
Adult↗
Delivered dialysis dose is suboptimal in hospitalized patients.
Underdialyzed patients have high hospitalization and mortality rates. It is unclear if such patients receive adequate dialysis during hospitalization. In this cross-sectional study, we evaluated single treatment delivered dialysis dose during hospitalization and compared this to the dosage received at the free-standing outpatient clinics in the same patients. Eighty-four patients (54% male) aged 23-63 years (means +/- SD 55.5 +/- 14.6) who have been on dialysis for at least 3 months were evaluated. Hypertension and diabetes were the most common diagnoses, while thrombosed graft or fistula accounted for 40% of admissions. The mean dialysis treatment time (Td) was 30 min longer in the outpatient (OP) setting than the hospital (H): 3.6 +/- 0.3 vs. 3.1 +/- 0.2 h (p < 0.0001). Attained blood flow (QB) was 15% greater in the OP than H: 394 +/- 40 vs. 331 +/- 54 ml/min (p < 0.0001). The Kt/V was analyzed in 49 of 84 patients; the OP Kt/V was 20% greater than the H Kt/V: 1.38 +/- 0.2 vs. 1.11 +/- 0.1 (p < 0.0001). A further breakdown of H Kt/V according to access and membrane types showed that patients with functional grafts/fistula had a higher Kt/V than those with temporary accesses 1.14 +/- 0.1 vs. 1.07 +/- 0.1 (p = 0.01). We conclude that hospitalized patients receive suboptimal dialysis dose, this could have a negative impact on survival if hospitalization is recurrent and prolonged. Kinetic modeling should be routinely performed in such patients and Td should be increased in patients with temporary accesses.
Adult↗
Norian SRS cement augmentation in hip fracture treatment. Laboratory and initial clinical results.
Bone quality, initial fracture displacement, severity of fracture comminution, accuracy of fracture reduction, and the placement of the internal fixation device are important factors that affect fixation stability. New high strength cements that are susceptible to remodeling and replacement for fracture fixation may lead to improved clinical outcome in the treatment of hip fractures. Norian SRS is an injectable, fast setting cement that cures in vivo to form an osteoconductive carbonated apatite of high compressive strength (55 MPa) with chemical and physical characteristics similar to the mineral phase of bone. It can be used as a space filling internal fixation device to facilitate the geometric reconstruction, load transfer, and healing of bone with defects and/or fractures in regions of cancellous bone. Furthermore, this cement can improve the mechanical holding strength of conventional fixation devices. Use of this material potentially could improve fracture stability, retain anatomy during fracture healing and improve hip function, thus achieving better clinical outcomes. In vivo animal studies have shown the material's biocompatibility, and cadaveric studies have shown the biomechanical advantage of its use in hip fractures. Initial clinical experience (in 52 femoral neck fractures and 39 intertrochanteric fractures) showed the potential clinical use of this innovative cement in the treatment of hip fractures.
Aged↗
Prognostic significance of colony-stimulating factor receptor expression in ipsilateral breast cancer recurrence.
The macrophage colony-stimulating factor receptor (CSF-1R), the product of the c-fms proto-oncogene, regulates normal proliferation and differentiation of macrophages and trophoblasts. Recent research found abnormal expression of CSF-1R in human carcinomas of the breast, endometrium, and ovary. Furthermore, activation of CSF-1R by its ligand has been shown to regulate invasiveness and anchorage-independent growth in breast carcinoma cells. To study the significance of CSF-1R expression in breast cancer, we designed a case-controlled immunohistochemical study. We chose 80 patients from a database of 1200 early stage I or II breast cancer patients treated with conservative surgery and radiation therapy. Expression of CSF-1R in the tumors of 40 patients who experienced an ipsilateral breast tumor recurrence (IBTR) as a primary site of relapse were compared with 40 patients who had not experienced an IBTR. The index and control patients were matched by age, clinical stage, nodal status, and follow-up. Paraffin-embedded sections were immunostained with antibodies directed toward CSF-1R. For the CSF-1R antibody, a total of 28 index cases (70%) demonstrated strong staining, whereas only 16 control cases (40%) demonstrated high immunoreactivity (P = 0.007). The CSF-1R antibody showed a positive correlation for local relapse, but no correlation was found between CSF-1R expression and distant metastasis. In summary, our findings provide evidence for the poor prognostic role of CSF-1R in IBTR.
Adult↗
Insulin-like growth factor-I receptor overexpression mediates cellular radioresistance and local breast cancer recurrence after lumpectomy and radiation.
The insulin-like growth factor-I receptor (IGF-IR) plays a critical role in cell growth regulation and transformation. The radiosensitivity of NIH 3T3 fibroblasts overexpressing either wild-type or mutant IGF-IR was examined. High levels of wild-type IGF-IR conferred radioresistance, and mutational analysis revealed that this effect correlated with the transforming capacity but not the mitogenic activity of the receptor. The radioresistant phenotype was reversed when the cells were incubated with antisense oligonucleotides targeted to IGF-IR mRNA, demonstrating that IGF-IR directly influences radioresistance. The clinical significance of these findings was examined in an immunohistochemical analysis of primary breast tumors, revealing that high levels of IGF-IR in tumor samples were highly correlated with ipsilateral breast tumor recurrence (IBTR) following lumpectomy and radiation therapy (P = 0.001). Subgroup analysis revealed that, for early breast tumor relapses (within 4 years of initial breast tumor diagnosis), elevated levels of IGF-IR were strongly associated with IBTR (P = 0.004) but IGF-IR expression was not prognostic for IBTR from breast cancer patients with late relapses (P was not significant). These studies provide evidence for the influence of IGF-IR on cellular radioresistance and response to therapy and raise the possibility that the radiocurability of selected tumors may be improved by pharmaceutical strategies directed toward the IGF-IR.
3T3 Cells↗