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Monica E Lindgren,
Christopher P Fagundes,
Catherine M Alfano,
Stephen P Povoski, Doreen M Agnese,
Mark W Arnold,
William B Farrar,
Lisa D Yee,
William E Carson,
Carl R Schmidt,
Janice K Kiecolt-Glaser
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ABSTRACT: OBJECTIVE: A cancer diagnosis provokes significant levels of emotional distress, with intrusive thoughts being the most common manifestation among breast cancer survivors. Cancer-related intrusive thoughts can take the form of emotional memories, flashbacks, nightmares, and intrusive images. Emotional arousal after a severe life stressor prolongs adrenergic activation, which in turn may increase risk for post-traumatic symptomatology. However, antihypertensive beta-blockers block adrenergic activation and are known to reduce traumatic memories and related psychological distress. Thus, the current study examined the association between beta-blocker use and the severity of cancer-related intrusive thoughts and related symptoms following a cancer diagnosis. METHODS: The 174 breast and 36 female colorectal cancer patients who had recently undergone diagnostic screening or biopsy included 39 beta-blocker users and 171 non-users. Prior to any cancer treatment including surgery, participants completed questionnaires that included the Impact of Events Scale and the Center for Epidemiological Studies Depression Scale. Analyses controlled for age, education, cancer stage, cancer type, days since diagnosis, marital status, depression, and comorbidities. RESULTS: Although the high rates of cancer-related distress in this sample were similar to those of other studies with recently diagnosed patients, beta-blocker users endorsed 32% fewer cancer-related intrusive thoughts than non-users. CONCLUSIONS: Recently diagnosed cancer patients using beta-blockers reported less cancer-related psychological distress. These results suggest that beta-blocker use may benefit cancer patients' psychological adjustment following diagnosis, and provide a promising direction for future investigations on the pharmacological benefits of beta-blockers for cancer-related distress. Copyright © 2012 John Wiley & Sons, Ltd.
Psycho-Oncology 12/2012; · 3.34 Impact Factor
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ABSTRACT: Background: CC49 is a monoclonal antibody directed against a pancarcinoma antigen (TAG-72) expressed by colorectal cancers. The use of
murine CC49 in radioimmunoguided surgery (RIGS) was problematic because of the human anti-mouse antibodies (HAMA) generated.
This study was designed to assess the clearance, safety, and effectiveness of localization of a complimentarity determining
region (CDR)-grafted humanized domain-deleted antitumor CC49 antibody (HuCC49°CH2).
Methods: After thyroid blockade, 1 mg of HuCC49°CH2 radiolabeled with 2 mCi of iodine-125 was administered. All patients subsequently underwent traditional exploration followed
by a survey with the gamma-detecting probe. In five patients, exploration was performed 10 to 24 days after injection, when
precordial counts were sufficiently low (<30 counts per 2 seconds [cp2s]). Traditionally suggestive and probe-positive tissue
was biopsied or excised and examined for the presence of carcinoma, when considered appropriate by the operating surgeon.
Serum was assessed for HAMA.
Results: Seventeen sites were identified as suggestive of carcinoma on traditional exploration and 21 by RIGS. Of these, pathologic
correlation was obtained in 15. The sensitivity of RIGS was 92%, and the positive predictive value was 100%. None of the patients
expressed significant HAMA.
Conclusions: This initial study indicates that the HuCC49°CH2 monoclonal antibody, when used with RIGS, is safe and sensitive in detecting recurrent intra-abdominal colon cancer.
Annals of Surgical Oncology 04/2012; 11(2):197-202. · 4.17 Impact Factor
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Christopher P Fagundes,
Ronald Glaser,
Catherine M Alfano,
Jeanette M Bennett,
Stephen P Povoski,
Adele M Lipari, Doreen M Agnese,
Lisa D Yee,
William E Carson,
William B Farrar,
William B Malarkey,
Janice K Kiecolt-Glaser
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ABSTRACT: Fatigue is a notable clinical problem in cancer survivors, and understanding its pathophysiology is important. The current study sought to determine biomarkers of fatigue that exist before cancer treatment. Relationships between the expression of latent Epstein-Barr virus (EBV) and cytomegalovirus (CMV) and fatigue were examined in 158 women newly diagnosed with breast cancer or awaiting a positive diagnostic result. Higher CMV antibody titers, but not EBV antibody titers, were associated with a greater likelihood of being fatigued. Associations between fatigue and higher CMV antibody titers remained after controlling for alcohol use, smoking, comorbidities, depressive symptoms, age, BMI, cancer stage, and sleep problems. More sleep problems and higher levels of depressive symptoms were also associated with a greater likelihood of being fatigued. CMV antibody titers, but not EBV antibody titers, were associated with higher levels of C-reactive protein (CRP), but CRP was not associated with fatigue. When the cellular immune system is compromised, reactivation of latent herpesviruses may fuel chronic inflammatory responses. Prior work has suggested that fatigue may be related to inflammation and its associated sickness behaviors; accordingly, our findings may be tapping into this same physiological substrate.
Brain Behavior and Immunity 03/2012; 26(3):394-400. · 4.72 Impact Factor
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Christopher P Fagundes,
Jeanette M Bennett,
Catherine M Alfano,
Ronald Glaser,
Stephen P Povoski,
Adele M Lipari, Doreen M Agnese,
Lisa D Yee,
William E Carson,
William B Farrar,
William B Malarkey,
Min Chen,
Janice K Kiecolt-Glaser
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ABSTRACT: Both higher socioeconomic status (SES) and supportive personal relationships confer health benefits, including better immune function. This study assessed the joint impact of SES and social support on the expression of a latent herpesvirus, Epstein-Barr virus (EBV), in a group of highly stressed women.
Two-hundred and twenty four women either awaiting further evaluation following an abnormal mammogram or newly diagnosed with breast cancer completed questionnaires and provided blood samples to assess EBV viral capsid antigen (VCA) IgG antibody titers.
More highly educated women with more support from friends had lower EBV VCA antibody titers, reflecting a stronger cellular immune response to the latent virus; however, among less educated women, friend support was not associated with EBV antibody titers. As revealed in an ancillary analysis, more highly educated women with more friend support had lower systolic blood pressure (SBP); however, friend support was not associated with SBP among less educated women. Neither depression nor perceived stress mediated these associations. Neither cancer status nor cancer stage among those diagnosed with cancer was significantly related to these outcomes.
Lower SES women may not reap the same immunological benefits from friend support when experiencing a stressful life event as their higher SES counterparts.
Health Psychology 01/2012; 31(1):11-9. · 3.87 Impact Factor
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ABSTRACT: To determine whether, in the era of sentinel lymph node (SLN) biopsy, head and neck melanoma (HNM) has a poorer outcome than melanomas at other sites (OMS).
Prospective database, 1994 to 2004. Characteristics and outcomes of patients with HNM vs those with OMS were analyzed by Fisher test, paired t test, and chi(2) test.
Tertiary referral center.
A total of 755 patients with melanoma who had undergone SLN biopsy.
Differences between patients with HNM and those with OMS.
A total of 17.4% of patients had HNM vs 82.6% with OMS. There was a male HNM preponderance: 68.7% vs 50.3% for females (P < .01). Patients with HNM were older (mean [SD] age, 57.1 [16.6] years vs 53.3 [16.2] years; P < .01). There were fewer cases of superficial spreading melanoma in patients with HNM (29.0% vs 53.7%; P < .01). There were more diagnoses of lentigo maligna in patients with HNM (26.0% vs 1.9%; P < .01). The mean thickness of the primary lesion was 2.32 (1.9) mm vs 2.31 (2.9) mm; P = .49. Fewer patients with HNM had Clark level involvement lower than level IV (13.3% vs 24.0%; P < .01). More SLNs were harvested from patients with HNM (3.72 [3.2] vs 2.89 [2.6]; P < .01), but a lower percentage of positive SLNs was found (9.2% vs 16.0%; P < .05). There was no difference in local, regional, or distant recurrence (5.3%, 6.9%, and 5.3%, respectively, in patients with HNM and 3.4%, 5.5%, and 6.7%, respectively, in patients with OMS). The 2- and 5-year survival rates for patients with HNM were 96.2% and 72.6%, respectively, vs 93.6% and 79.0%, respectively, in patients with OMS (P = .40).
Most patients with HNM are older males with more SLNs harvested. They do not seem to have poorer outcome than patients with OMS.
Archives of Otolaryngology - Head and Neck Surgery 11/2007; 133(11):1121-4. · 1.63 Impact Factor
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ABSTRACT: Although breast cancer is relatively common, only about 5% of cases are due to inheritance of highly penetrant cancer susceptibility genes. The majority of these are caused by mutations in the BRCA1 and BRCA2 genes, which are also associated with an increased risk of ovarian cancer. Increased surveillance, chemoprevention, and prophylactic surgeries are standard options for the effective medical management of mutation carriers. However, optimal management of female carriers who choose to undergo prophylactic surgeries is still poorly understood.
The authors provide an overview of the current literature regarding medical management options for women carriers of BRCA1 and BRCA2 gene mutations and the implications for those individuals who have chosen to undergo prophylactic surgeries.
BRCA mutation carriers who opt for prophylactic surgeries are still at risk for development of malignancy, and appropriate monitoring is warranted.
There are limited data on the appropriate medical management for BRCA mutation carriers after prophylactic surgeries. However, a management plan can be extrapolated from the general management recommendations for surveillance and other risk-reducing strategies in BRCA-positive individuals.
Cancer control: journal of the Moffitt Cancer Center 11/2007; 14(4):330-7.
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ABSTRACT: Although sentinel lymph node (SLN) biopsy is a standard of care for the evaluation of the axillary lymph nodes during breast cancer surgery, a substantial degree of variation exists among individual surgeons as to what represents an adequate assessment. The aim of the current study was to assess when metastatic disease was first identified within consecutively harvested SLN candidates for invasive breast cancers demonstrating a positive SLN.
We retrospectively analyzed a series of 400 breast cancers from a recently published prospective randomized clinical trial. A combined radiocolloid and blue dye technique was used. All potential SLN candidates, containing counts of at least 10% of the hottest SLN and/or containing blue dye, were harvested and were consecutively numbered in the order of the decreasing level of counts (with the hottest SLN representing SLN #1).
Among 371 invasive breast cancers, a SLN was identified within 353 cases (95%). Mean number of SLNs identified was 2.5 (range, 1 to 9), with a single SLN identified in 104 (29%) cases, two identified in 110 (31%), three identified in 73 (21%), four identified in 35 (10%), five identified in 16 (5%), and six or more identified in 15 (4%). A positive SLN was found in 104 (29%) cases. SLN #1 was the first positive SLN in 86 (83%). SLN #2 was the first positive SLN in 15 (14%). SLN #3, SLN #4, and SLN #5 were the first positive SLN in one case (1%) each. A positive SLN was found in 18% (19/104) of cases when a single SLN was identified, as compared to in 34% (85/249) when two or more SLNs were identified (P = 0.003).
The accurate and optimal assessment of the axilla during breast cancer surgery requires persistence and diligence for attempting to identify all potential SLN candidates in order to avoid failing to recognize a positive SLN. The scenario in which only a single negative SLN candidate is intraoperatively identified is one that should raise some concern to the operating surgeon.
World Journal of Surgical Oncology 02/2007; 5:18. · 1.12 Impact Factor
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Stephen P Povoski,
Johannes O Olsen,
Donn C Young,
Johannah Clarke,
William E Burak,
Michael J Walker,
William E Carson,
Lisa D Yee, Doreen M Agnese,
Rodney V Pozderac,
Nathan C Hall,
William B Farrar
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ABSTRACT: Multiple injection routes, including intradermal (ID), intraparenchymal (IP), and subareolar (SA), are used for 99mTc-sulfur colloid administration for sentinel lymph node (SLN) mapping and biopsy in breast cancer. The aim of this study was to compare localization by ID, IP, and SA injection routes based on preoperative lymphoscintigraphy and intraoperative identification.
Four hundred prospectively randomized breast cancers underwent SLN mapping and biopsy.
Preoperative lymphoscintigraphy demonstrated localization to the axilla in 126/133 (95%) ID, 82/132 (62%) IP, and 96/133 (72%) SA (P < 0.001 ID vs. IP and ID vs. SA; P = 0.081 IP vs. SA), with a mean duration of preoperative lymphoscintigraphy of 139 +/- 18 minutes. Mean time to first localization when localization was demonstrated on preoperative lymphoscintigraphy was 8 +/- 14 minutes for ID, 53 +/- 49 for IP, and 22 +/- 29 for SA (P < 0.001 ID vs. IP and ID vs. SA; P = 0.003 IP vs. SA). Intraoperative identification of a SLN at the time of SLN biopsy was successful in 133/133 (100%) ID, 121/134 (90%) IP, and 126/133 (95%) SA (P < 0.001 ID vs IP; P = 0.014 ID vs. SA; P = 0.168 IP vs. SA), with a mean time from injection of 99mTc-sulfur colloid to start of SLN biopsy of 288 +/- 71 minutes. Mean intraoperative time to harvest the first SLN was 9 +/- 4 minutes for ID, 13 +/- 6 for IP, and 12 +/- 6 for SA (P < 0.001 ID vs. IP and ID vs. SA; P = 0.410 IP vs. SA).
The ID injection route demonstrated a significantly greater frequency of localization, decreased time to first localization on preoperative lymphoscintigraphy, and decreased time to harvest the first SLN. This represents the first prospective randomized clinical trial to confirm superiority of the ID route for administration of 99mTc-sulfur colloid during SLN mapping and biopsy in breast cancer.
Annals of Surgical Oncology 12/2006; 13(11):1412-21. · 4.17 Impact Factor
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Doreen M Agnese
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ABSTRACT: Although mammography remains the most widely used tool for the early detection of breast cancers and evaluation of palpable abnormalities, a number of other imaging tools are being developed and used. Ultrasonography (US) is an excellent adjunct to conventional mammography. In addition to identifying solid and cystic abnormalities, US can often distinguish benign and malignant solid nodules. Magnetic resonance imaging (MRI) also is useful in assessing the extent of disease within the breast, particularly in women with dense breasts. MRI may be a more sensitive screening tool in women at elevated breast cancer risk. Newer techniques based on the metabolic activity of breast tumors also have been developed. One such technique is scintimammography, which uses radiolabeled tracers to detect breast malignancies. Positron emission tomography (PET), which relies on the high metabolic rate of tumors, also has been described as a method to evaluate breast disease. Other techniques, such as optical tomography and thermography, rely on angiogenesis and generated heat to identify cancers. These and other tools may help to improve both the sensitivity and specificity of cancer detection. Ideally, this improved detection results in improved outcomes in those who have breast cancer and avoidance of unnecessary procedures in those who do not.
Surgical technology international 02/2005; 14:51-6.
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Current Problems in Surgery 12/2004; 41(11):882-935. · 2.33 Impact Factor
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ABSTRACT: This study sought to determine the differences in presentation and treatment of young women (< or =40 years of age) with breast cancer.
A prospective database was analyzed for differences in presentation and care in breast cancer patients < or =40 and >40 years of age.
The study group consisted of 1685 women. Younger women were more likely to present with a palpable mass, have estrogen receptor/progesterone receptor (ER/PR)-negative tumors, and have more advanced disease at presentation. Although there was no difference in breast conservation rates, younger women were more likely to have postmastectomy reconstruction. Younger women were more likely to receive chemotherapy, even with node-negative tumors less than 1 cm in diameter (37% vs. 13%, P = 0.01).
The presentation of younger women with breast cancer differs from that of older women. Although the surgical management is similar, adjuvant therapy differs, with younger women more likely to be treated with chemotherapy.
The American Journal of Surgery 10/2004; 188(4):437-9. · 2.78 Impact Factor
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ABSTRACT: CC49 is a monoclonal antibody directed against a pancarcinoma antigen (TAG-72) expressed by colorectal cancers. The use of murine CC49 in radioimmunoguided surgery (RIGS) was problematic because of the human anti-mouse antibodies (HAMA) generated. This study was designed to assess the clearance, safety, and effectiveness of localization of a complimentarity determining region (CDR)-grafted humanized domain-deleted antitumor CC49 antibody (HuCC49DeltaCH2).
After thyroid blockade, 1 mg of HuCC49DeltaCH2 radiolabeled with 2 mCi of iodine-125 was administered. All patients subsequently underwent traditional exploration followed by a survey with the gamma-detecting probe. In five patients, exploration was performed 10 to 24 days after injection, when precordial counts were sufficiently low (<30 counts per 2 seconds [cp2s]). Traditionally suggestive and probe-positive tissue was biopsied or excised and examined for the presence of carcinoma, when considered appropriate by the operating surgeon. Serum was assessed for HAMA.
Seventeen sites were identified as suggestive of carcinoma on traditional exploration and 21 by RIGS. Of these, pathologic correlation was obtained in 15. The sensitivity of RIGS was 92%, and the positive predictive value was 100%. None of the patients expressed significant HAMA.
This initial study indicates that the HuCC49DeltaCH2 monoclonal antibody, when used with RIGS, is safe and sensitive in detecting recurrent intra-abdominal colon cancer.
Annals of Surgical Oncology 02/2004; 11(2):197-202. · 4.17 Impact Factor
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ABSTRACT: Radiofrequency ablation (RFA) is gaining acceptance as a treatment modality for several tumor types. However, its use in patients with breast carcinoma remains investigational. The current study was undertaken to determine the feasibility of treating small breast malignancies with RFA and to evaluate the postablation magnetic resonance imaging scans (MRI) and histologic findings.
Patients with core-needle biopsy-proven invasive carcinoma (< 2 cm in greatest dimension) underwent ultrasound-guided RFA under local anesthesia. Surgical excision was undertaken 1-3 weeks later. All patients had breast MRI scans performed before ablation and repeated within 24 hours of surgery.
Ten patients completed the treatment and experienced minimal or no discomfort. The mean tumor size was 1.2 cm (range, 0.8-1.6 cm). The mean time required for ablation was 13.8 minutes (range, 7-21 minutes). There were no treatment-related complications other than minimal breast ecchymosis. A pre-RFA MRI scan showed enhancing tumors in 9 of 10 (90%) patients. A post-RFA MRI scan revealed no residual lesion enhancement in 8 of these 9 patients (89%), and the zone of ablation was demonstrated in all patients. One patient had residual enhancement anteriorly consistent with residual tumor, which was confirmed histologically. Evaluation of the remaining ablated lesions revealed a spectrum of changes ranging from no residual tumor to coagulation necrosis with recognizable malignant cells. Immunostains for cytokeratin 8/18 were negative in these recognizable malignant cells.
RFA of small breast malignancies can be performed under local anesthesia in an office-based setting. A postablation MRI scan appears to predict histologic findings, although tumor viability needs to be assessed in a long-term study.
Cancer 11/2003; 98(7):1369-76. · 4.77 Impact Factor
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ABSTRACT: The lipopolysaccharide (LPS) receptor complex consists of two interacting receptors (CD14 and TLR4) and an associated protein (MD-2). When engaged by LPS, as in gram-negative infection, this complex transduces a signal detected by MyD88 and passed onward by a cascade of the IRAKs, TRAF6, and NIK, resulting in activation of NF-kappaB. A similar cascade, mediated by TLR2, occurs with ligands derived from gram-positive bacteria. In vitro studies of human monocytes have shown that TLR4 mRNA is paradoxically upregulated in response to "tolerizing" doses of LPS. This study evaluated changes in vivo of blood monocyte CD14, TLR4, TLR2, and MD-2 mRNA by reverse transcription followed by real-time polymerase chain reaction in surgical intensive care unit patients and in normal controls. In addition cell-surface receptor expression of TLR2, TLR4, and CD14 was assessed by flow cytometry in patients and normal controls. Inflammation-induced acute tolerance to LPS was evaluated by ex vivo whole blood tumor necrosis factor alpha production and was significantly reduced in patients compared with controls, confirming LPS hyporesponsiveness. Monocyte mRNA and cell-surface receptor expression of TLR4 were increased 2.4-fold (P < 0.05) and 1.7-fold (P <.002), respectively, in patients compared with normal controls. Monocyte TLR2 mRNA, MD-2 mRNA and CD14 and TLR2 cell-surface expression were not significantly changed compared with controls. The present study suggests that the acute inflammatory condition associated with peripheral cellular LPS hyporesponsiveness is neither specific to prior infectious challenge nor can be ascribed to significant alterations in expression of the cell-surface LPS binding complex proteins.
Shock 11/2003; 20(5):415-9. · 2.85 Impact Factor
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ABSTRACT: Consideration of sentinel lymph node biopsy (SLNB) is recommended for thin melanomas with poor prognostic features; however, few metastases are identified. The purpose of this study was to assess the cost effectiveness of SLNB in this population.
The prospective melanoma database was reviewed to identify patients with melanomas <1.2 mm thick who had undergone SLNB. Physician and hospital charges were collected from the appropriate billing department.
A total of 138 patients were identified over an 8-year period (1994-2002). Two patients with positive SLNs were identified (1.4%), one with a melanoma <1 mm thick. Patient charges for SLNB ranged from $10,096 to $15,223 US dollars, compared with $1000 to $1740 US dollars for wide excision as an outpatient. Using these charges, the cost to identify a single positive SLN would be between $696,600 and $1,051,100 US dollars. The cost for wide excision would be between $69,000 and $120,100 US dollars. Assuming that all patients with a positive SLN would die of melanoma, the cost per life saved would be $627,000 to $931,000 US dollars.
The cost of performing SLNB in this population is great and only a small number will have disease identified that will alter treatment. These data call into question the appropriateness of SLNB for thin melanomas.
Surgery 10/2003; 134(4):542-7; discussion 547-8. · 3.10 Impact Factor
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ABSTRACT: Tumor necrosis factor-alpha (TNF-alpha) is a well-documented central inflammatory mediator in sepsis. Specific polymorphisms of the TNF-alpha and TNF-beta genes (TNF2 and LTA + 250, respectively) have been suggested to correlate with higher mortality in septic shock. This study sought to determine whether these polymorphisms of the TNF-alpha and -beta genes are associated with an increased risk of infection in an at-risk surgical intensive care population.
Forty-four consecutive patients with systemic inflammatory response syndrome were enrolled prospectively in the study. Genomic DNA was isolated from whole blood samples using standard phenol/chloroform extraction techniques. Specific fragments including the polymorphic sites of each gene were amplified by polymerase chain reaction, and restriction enzyme digestions were performed. Genotypes were determined by gel electrophoresis and confirmed by direct sequencing.
Eighty-six percent of the patients were TNF1 homozygotes (G:G at -308 of the TNF-alpha promoter region), whereas 9% of the patients were homozygous for TNF2 (A:A). There was no difference in the incidence of sepsis, septic shock, or mortality between patients bearing the various alleles. Only 13.6% of the patients exhibited the G:G alleles for TNF-beta, whereas the homozygous A:A was present in 45.4% of the patients.
The presence of the A allele at these polymorphic sites did not predispose critically ill surgical patients to either infection or septic shock.
Surgical Infections 02/2003; 4(2):163-9. · 1.80 Impact Factor
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ABSTRACT: Human toll-like receptor 4 (hTLR4) and CD14 are known to be components of the lipopolysaccharide receptor complex. Our study investigated the association between TLR4 mutations (Asp299Gly and Thr399Ile) and CD14 polymorphism(s) with outcome in an intensive care unit (ICU) population at risk for sepsis. By use of a polymerase chain reaction-based restriction fragment-length polymorphism analysis technique, the hTLR4 gene was altered in 14 (18%) of 77 ICU patients (all positive for systemic inflammatory response syndrome) and in 5 (13%) of 39 volunteers. There was a significantly higher incidence of gram-negative infection among patients with the mutations (11 [79%] of 14), compared with that in the wild-type population (11 [17%] of 63; P=.004). No association between CD14 polymorphism(s) and the incidence of infection or outcome was observed. These findings indicate that hTLR4 mutations are associated with an increased incidence of gram-negative infections in critically ill patients in a surgical setting.
The Journal of Infectious Diseases 12/2002; 186(10):1522-5. · 6.41 Impact Factor
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ABSTRACT: Lipopolysaccharide (LPS) is a potent activator of human monocytic cells. We have determined that LPS stimulation of the human monocytic cell line, THP-1, results in an increased apoptotic rate. We hypothesized that cDNA expression array analysis could be used to identify target genes involved in the regulation of this process.
THP-1 cells (1 x 10(6)/mL) were stimulated with LPS (1 microg/mL) or vehicle control. Apoptosis was measured at 0, 24, 48, 72 and 96 h using propidium iodide staining and flow cytometry to determine the percentage of cells with hypodiploid DNA. At 16 h, the Atlas Human cDNA expression array system, containing probes for 205 genes related to apoptosis, was used to survey and quantify transcript expression. The experiment was performed in duplicate and the membranes were normalized to cytoplasmic beta-actin. Standard Western blotting was performed on the conditioned medium to correlate secreted protein expression with RNA expression. Pretreatment with insulin-like growth factor I (IGF-I) was performed to determine whether the effects of insulin-like growth factor binding protein-3 (IGFBP-3) on apoptosis were IGF-dependent.
LPS stimulation of THP-1 cells resulted in a greater than 2-fold increase in the rate of apoptosis when compared to vehicle control. When the cDNA expression arrays were compared, there was a 500-fold increase in the expression of the IGFBP-3 transcript in the LPS-stimulated cells. Western blotting of culture medium verified an approximately 2-fold increase in secreted IGFBP-3. Pretreatment with IGF-I did not prevent the increase in apoptosis seen with LPS stimulation.
THP-1 cell apoptosis is increased in response to LPS stimulation and is associated with a significant induction of IGFBP-3 mRNA and protein. IGFBP-3, which reportedly promotes apoptosis and modulates the bioavailability of the pro-survival insulin-like growth factor 1, may serve to regulate apoptosis in monocytic cells in an IGF-independent manner. These data further support the investigation of the role of the IGF axis in programmed cell death of immune cells.
Surgical Infections 02/2002; 3(2):119-25; discussion 125-6. · 1.80 Impact Factor
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ABSTRACT: With the improvements in imaging techniques that have allowed the earlier detection of smaller breast cancers and the desire for improvements in cosmetic outcome, a number of minimally invasive techniques for the treatment of early stage breast cancers are being investigated. Ablative therapies, including laser ablation, focused ultrasound, microwave ablation, radiofrequency ablation, and cryoablation, have been described. All of these techniques have shown promise in the treatment of small cancers of the breast; however, additional research is needed to determine the efficacy of these techniques when they are used as the sole therapy and to determine the long-term local recurrence rates and survival associated with these treatment strategies.
The Cancer Journal 11(1):77-82. · 3.26 Impact Factor
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The Breast Journal 9(6):501-2. · 1.64 Impact Factor
