Biomedical subjects

S Korourian

Publications and source records attributed to S Korourian.

At least 19 recordsLinked to original sources

PubMed2001

Polymorphisms in glutathione S-transferases (GSTM1 and GSTT1) and survival after treatment for breast cancer.

The response to treatment for breast cancer is likely predicted by a number of disease and tumor tissue characteristics, many of which are under active investigation. One area that has received little attention is that of endogenous capabilities to respond to reactive oxygen species and subsequent byproducts resulting from radiation therapy and a number of chemotherapeutic agents, preventing cytotoxicity toward tumor cells. The glutathione S-transferases are key conjugating enzymes in this response, and GSTM1 and GSTT1 have deletion polymorphisms that result in no enzyme activity. In this retrospective study, we evaluated the role of GSTM1- and GSTT1-null genotypes on disease-free and overall survival among 251 women who received treatment for incident, primary breast cancer. Women were identified through Tumor Registry records and normal archived tissue retrieved for genotyping. Adjusting for age, race, and stage at diagnosis, women with null genotypes for GSTM1 and GSTT1 had reduced hazard of death [adjusted hazard ratio (HR), 0.59; 95% confidence interval (CI), 0.36-0.97; and HR, 0.51; CI, 0.29-0.90, respectively] in relation to those with alleles present. Furthermore, women who were null for both GSTM1 and GSTT1 had one-third the hazard of death of those with alleles for both genes present (adjusted HR, 0.28; 95% CI, 0.11-0.70). Similar relationships were noted for risk of recurrence. These data indicate that interindividual differences in activity of enzymes that prevent therapy-generated reactive oxidant damage may have an important impact on disease recurrence and overall survival.

Adult↗

PubMed2001

Soy protein isolate consumption protects against azoxymethane-induced colon tumors in male rats.

Male Sprague-Dawley rats (F2 generation) that had been fed modified American Institute of Nutrition-93G diets formulated with a single protein source of either casein or soy protein isolate for their entire life received azoxymethane once a week for 2 weeks (s.c., 15 mg/kg) starting at age 90 days. Forty weeks later, all rats were euthanized, the colon was examined visually for masses and these were subsequently evaluated histologically. Rats fed the casein diet had a 50% incidence of colon tumors compared with 12% on soy protein-based diets (P<0.05). These results suggest that consumption of soy protein-containing diets may reduce the risk of developing colon tumors.

Adenocarcinoma↗

PubMed2001

Plasma cells in chronic endometritis are easily identified when stained with syndecan-1.

BACKGROUND: Chronic endometritis has been observed in 3-10% of women with irregular uterine bleeding who undergo endometrial biopsy. The diagnosis of chronic endometritis rests on the recognition of plasma cells in endometrial tissue that may show a prominent spindle cell stromal component, and is frequently difficult to date. Syndecan-1 is a cell-surface proteoglycan that is expressed on the cell surface of plasma cells. DESIGN: Eighteen endometrial curettage cases with the diagnosis of chronic endometritis and 25 endometrial curettage cases of dysfunctional uterine bleeding, in females under the age of thirty-five in whom no other histopathologic changes were noted, were reviewed for the presence of plasma cells. Sections were then stained with syndecan-1. RESULTS: All of the chronic endometritis cases showed easily visible syndecan-1 staining of plasma cell membranes. None of the cases of dysfunctional uterine bleeding showed presence of plasma cells in either the hematoxylin and eosin stained or syndecan-1 stained sections. CONCLUSIONS: In cases of suspected chronic endometritis in which no plasma cells can be found on hematoxylin and eosin stained slides, syndecan-1 may be an effective adjunct in the identification of plasma cells and thus aid in the diagnosis of chronic endometritis.

Chronic Disease↗

PubMed2001

Hematoma-directed ultrasound-guided breast biopsy.

OBJECTIVE AND SUMMARY BACKGROUND DATA: The standard technique for removal of nonpalpable breast lesions is needle localization breast biopsy. Because traumatic hematomas can often be seen with ultrasound, the authors hypothesized that iatrogenically induced hematomas could be used to guide the excision of nonpalpable lesions using ultrasound. METHODS: Twenty patients with nonpalpable breast lesions detected by magnetic resonance imaging only were enrolled in this single-institution trial, approved by the institutional review board. A hematoma consisting of 2 to 5 mL of the patient's own blood was injected into the breast to target the nonpalpable lesion. Intraoperative ultrasound of the hematoma was used to direct the excisional biopsy. RESULTS: The average age of women was 53.8 +/- 10 years. Ninety-five percent of lesions detected by magnetic resonance imaging were localized by hematoma injection. All the hematomas used to recognize targeted lesions were identified at surgery by ultrasound and removed without complication. Eight (40%) of the lesions were malignant, with an average tumor size of 12 +/- 6 mm (range 4-25). The remaining 12 lesions (60%) comprised papillomas, sclerosing adenosis, radial scar, fibroadenoma, and areas of atypical ductal hyperplasia. CONCLUSION: The results of this pilot study show the effectiveness of hematoma-directed ultrasound-guided breast biopsy for nonpalpable lesions seen by magnetic resonance imaging. This new procedure is potentially more comfortable for the patient because no wire or needle is left in the breast. It is technically faster and easier because ultrasound is used to visualize directly the location of the hematoma at surgery and to confirm lesion removal in the operating room by specimen ultrasound. The hematoma can be placed several days before biopsy, easing scheduling, and without fear of the migration that may occur with needle localization. This method may have ready application to mammographically detected lesions.

Adult↗

PubMed2001

Dietary whey protein protects against azoxymethane-induced colon tumors in male rats.

Epidemiological studies have suggested a relationship between diet and colon cancer incidence. Results from animal studies suggest that whey protein, but not casein protein, may provide protective effects against experimentally induced breast cancer in animals. In the current study, we investigated the effects of casein and whey diets on chemically induced colon cancer in male rats. Pregnant female Sprague Dawley rats (days 3-4 of gestation) were maintained on modified AIN-93G diets formulated with a single protein source of either casein or whey. Life-time exposure to these diets was studied in the F1 generation (experiment A) or the F2 generation (experiment B). Male offspring were weaned to the same diets as the dams and were maintained on these diets throughout the study. At age 90 days, all rats received azoxymethane once a week for 2 weeks (s.c., 15 mg/kg). Forty weeks after the last azoxymethane injection, all rats were euthanized, the colon was examined visually for tumors, and each tumor was histologically evaluated. The weights and distribution of all of the tumors were recorded. In experiment A, rats fed the casein diet had a 56% incidence of colon tumors compared with 30% of the rats on whey-based diets (P < 0.05). In experiment B, rats fed the casein diet had 50% incidence of colon tumors compared with 29% in the whey group (P < 0.05). There were no significant effects of diet on tumor multiplicity or mass. These results suggest that consumption of whey protein-containing diets may reduce the risk of developing colon tumors.

Animals↗

PubMed2000

Association between survival after treatment for breast cancer and glutathione S-transferase P1 Ile105Val polymorphism.

A glutathione S-transferase (GST) P1 polymorphism results in an amino acid substitution, Ile105Val; the Val-containing enzyme has reduced activity toward alkylating agents. Cancer patients with the variant enzyme may differ in removal of treatment agents and in outcomes of therapy. We evaluated survival according to GSTP1 genotype among women (n = 240) treated for breast cancer. Women with the low-activity Val/Val genotype had better survival. Compared with Ile/Ile, hazard ratios for overall survival were 0.8 (95% confidence interval, 0.5-1.3) for Ile/Val and 0.3 (95% confidence interval, 0.1-1.0) for Val/Val (P for trend = 0.04). Inherited metabolic variability may influence treatment outcomes.

Adult↗

PubMed2000

Intraoperative ultrasound-guided breast biopsy.

BACKGROUND: Biopsy of nonpalpable lesions has increased during the last decade. Commonly these lesions are excised using preoperative wire localization. We describe a technique of intraoperative ultrasound-guided breast biopsy that allows easier excision and aids in obtaining surgical margins in breast cancer. METHODS: Intraoperative ultrasound was performed on 81 lesions. Ultrasound was used in an attempt to approximate a 1 cm margin on malignant lesions. RESULTS: All attempts to localize lesions with ultrasound in surgery were successful (81 of 81). Ultrasound-guided surgery was accurate in predicting margins in 24 of 25 malignant lesions. No complications resulted. CONCLUSION: Ultrasound proved to be an effective technique for localizing and excising breast lesions. Benefits may include improving patient comfort, avoiding complications of needle localization breast biopsy, and simplifying the scheduling of surgical procedures. Additionally, this procedure may be used to obtain adequate surgical margins and thus reduce the recurrence rate of breast cancer.

Adult↗

PubMed2000

Correlation of neural cell adhesion molecules with perineural spread of squamous cell carcinoma of the head and neck.

Perineural spread (PNS) is a poor prognostic factor associated with increased risk of local recurrence and nodal metastasis and reduced survival of patients with squamous cell carcinoma of the head and neck (SCCHN). There is some evidence to indicate that neural cell adhesion molecules (NCAMs) may play a role in PNS of a variety of tumor types. We performed this study to investigate whether NCAM expression can be used as a predictor of PNS in SCCHN. The surgical specimens of 66 patients with SCCHN were evaluated with monoclonal IgG antibody immunoperoxidase staining for NCAM. Of the 41 specimens with PNS, 38 (93%) showed evidence of NCAM expression. In contrast, only 9 specimens (36%) without PNS expressed NCAMs. The difference in NCAM expression between the study and control groups was statistically significant (P < 0.01).

Adult↗

PubMed2000

Neural cell adhesion molecule expression in adenoid cystic carcinoma of the head and neck.

OBJECTIVE: To investigate whether there is a correlation between neural cell adhesion molecule (NCAM) expression and perineural spread in patients with adenoid cystic carcinoma of the head and neck (ACCHN). STUDY DESIGN: Retrospective review of medical records and immunohistochemical staining of specimens from 37 patients treated at the University of Arkansas in Little Rock from 1987 to 1997. METHODS: Sections from paraffin-embedded specimens were examined for the presence of NCAM using monoclonal anti-NCAM antibody by avidin-biotin-peroxidase immunohistochemical staining. NCAM staining was scored in each specimen and correlated with the data obtained from patient charts. RESULTS: Twenty-five of 37 specimens (68%) showed histopathological evidence of perineural spread. All 37 specimens (100%) stained positive for NCAM, regardless of perineural spread status. CONCLUSION: Our results suggested that the use of NCAM expression as a predictor of perineural spread is highly unlikely.

Adult↗

PubMed2000

Diets containing whey proteins or soy protein isolate protect against 7,12-dimethylbenz(a)anthracene-induced mammary tumors in female rats.

A study was conducted to determine the protective effects of two common dietary proteins, soy protein isolate (soy) and bovine whey, against chemically induced mammary tumors in female Sprague Dawley rats. Rats were fed AIN-93G diets having casein, soy, or whey as the sole protein source. Rats within the same dietary groups were mated to obtain the F1 and F2 generations. At age 50 days, F1 (experiment A) or F2 (experiment B) female offspring (> or =19 rats/group) were p.o. gavaged with 80 mg/kg 7,12-dimethylbenz(a)anthracene, and mammary glands were evaluated when 100% of the casein-fed group developed at least one palpable tumor. Rats grew well on all three diets, but casein-fed rats gained slightly more body weight than soy- or whey-fed rats (P < 0.05). Vaginal opening occurred 1 day earlier in soy-fed rats than in casein- or whey-fed rats, but no other differences in reproductive and developmental parameters were observed between groups. When 50% of the casein-fed rats had at least one mammary tumor, lower tumor incidences (24-34%) were observed in the soy-fed (P < 0.009) and whey-fed groups (P < 0.001). When 100% of the casein-fed rats had at least one tumor, soy-fed rats had a lower tumor incidence (77%) in experiment B (P < 0.002), but not in experiment A (P < 0.12), and there were no differences in tumor multiplicity. Whey-fed rats had lower mammary tumor incidence (54-62%; P < 0.002) and multiplicity (P < 0.007) than casein-fed rats in both experiments. Our results indicate that diets rich in soy reduce the incidence of chemically induced mammary tumors by approximately 20%. Furthermore, whey appears to be at least twice as effective as soy in reducing both tumor incidence and multiplicity.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2000

Development, characterization and distribution of adoptively transferred peripheral blood lymphocytes primed by human papillomavirus 18 E7--pulsed autologous dendritic cells in a patient with metastatic adenocarcinoma of the uterine cervix.

We describe a 27-year-old woman with systemic chemoresistant and radioresistant metastatic disease secondary to a recurrence of human papillomavirus (HPV) 18 infected cervical adenocarcinoma of the uterine cervix who received adoptive transfer of peripheral blood T cells stimulated with HPV 18 E7-pulsed autologous dendritic cells (DC). Extensive in vitro characterization of the DC-activated T cells derived from peripheral blood mononuclear cells (PBMC) included phenotypic analysis, cytotoxicity and intracellular cytokine production. High cytotoxicity activity was observed by CD8+T cells against autologous tumor cells, but not against NK-sensitive K562 cells, autologous Con-A lymphoblasts, or autologous Epstein-Barr virus-transformed lymphoblastoid cells. Blocking studies demonstrated that lytic activity was significantly inhibited by pretreatment of tumor targets with MAb specific for HLA class I as well as that of effector cells with anti-CD8, anti-LFA-1, but not anti CD3 MAb. Two-color flow cytometric analysis of the cytotoxic T cells revealed that a significant proportion of CD8+ cells was also CD56+. These double positive CTLs were thymically derived, as shown by expression of heterodimeric CD8 molecules (alpha/beta CD8) and were endowed with high cytotoxic activity against tumor cells. Analysis of intracellular cytokine expression showed that the striking majority of E7-pulsed DC activated CD8+ T cells strongly expressed IFN-gamma, TNF-alpha and IL-2 but not IL-4. The patient received two infusions of cytotoxic tumor-specific T cells at 2 week intervals, and in vivo distribution of the T cells was followed by 111 oxine labeling and serial gamma camera imaging. Persistent accumulation of radioactivity in the lungs, which harbored extensive metastatic disease, was detected up to 120 hrs after the infusion. Taken together, these results illustrate the potential of E7-specific and tumor-specific CTL-based immunotherapy for the treatment of patients with invasive cervical cancer.

Adenocarcinoma↗

PubMed1999

Role of breast magnetic resonance imaging in determining breast as a source of unknown metastatic lymphadenopathy.

BACKGROUND: Occult primary breast cancer (OPBC) represents less than 1% of breast cancer. In only a third of cases, mammography identifies a primary tumor. We hypothesized that rotating delivery of excitation off-resonance breast magnetic resonance imaging (MRI) would identify or exclude the breast as a primary site in patients with OPBC. METHODS: In a retrospective review, 10 patients were identified with OPBC in which MRI was performed. Malignant appearing lesions were correlated with histopathologic findings at biopsy or surgery. RESULTS: MRI identified the primary site in 8 of 10 cases as breast (80%), and excluded it in 2 cases. The extent of disease and location was accurately predicted when compared with histopathologic specimen. CONCLUSIONS: As we continue to focus on a cure of early breast cancer, it is imperative that diagnostic images become more sensitive and specific. MRI accurately predicted OPBC in this subset of patients.

Adult↗

PubMed1999

Assessing margin status.

As little time ago as 1991 the NIH Consensus conference could not agree on the need for negative margins. Today, negative margin status has become a prerequisite for BCT recognizing that positive margins impact negatively on local recurrence rates. The science of margin evaluation is fast becoming recognized to play a key role in providing patients with the opportunity for breast conservation therapy as well as the best possible cosmetic result. Preoperative factors that predict a greater likelihood of failure to obtain margins such as larger tumor size and positive lymph nodes are fixed and can only be dealt with by taking larger biopsies. RODEO-MRI can preoperatively predict probability of success or failure and can actual better define tumor dimensions and extent and help plan excisions. Use of intraoperative US may be a future tool used to facilitate the excision of non-palpable and possibly palpable tumors. Intraoperative pathological assessment should not be performed by frozen section but consideration given to cytological assessment so as to allow feedback to the surgeon intraoperatively as to which margin needs more attention. Finally, using all the above methods of obtaining negative margins, the surgeon may have the ability to impact the outcome of breast cancer surgery and recurrence.

Biopsy, Needle↗

PubMed1999

Diet and risk of ethanol-induced hepatotoxicity: carbohydrate-fat relationships in rats.

Nutritional status is a primary factor in the effects of xenobiotics and may be an important consideration in development of safety standards and assessment of risk. One important xenobiotic consumed daily by millions of people worldwide is alcohol. Some adverse effects of ethanol, such as alcohol liver disease, have been linked to diet. For example, ethanol-induced hepatotoxicity in animal models requires diets that have a high percentage of the total calories as unsaturated fat. However, little attention has been given to the role of carbohydrates (or carbohydrate to fat ratio) in the effects of this important xenobiotic on liver injury. In the present study, adult male Sprague-Dawley rats (8-10/group) were infused (intragastrically) diets high in unsaturated fat (25 or 45% total calories), sufficient protein (16%) and ethanol (38%) in the presence or absence of adequate carbohydrate (21 or 2.5%) for 42-55 days (d). Animals infused ethanol-containing diets adequate in carbohydrate developed steatosis, but had no other signs of hepatic pathology. However, rats infused with the carbohydrate-deficient diet had a 4-fold increase in serum ALT levels (p < 0.05), an unexpectedly high (34-fold) induction of hepatic microsomal CYP2E1 apoprotein (p < 0.001), and focal necrosis. The strong positive association between low dietary carbohydrate, enhanced CYP2E1 induction and hepatic necrosis suggests that in the presence of low carbohydrate intake, ethanol induction of CYP2E1 is enhanced to levels sufficient to cause necrosis, possibly through reactive oxygen species and other free radicals generated by CYP2E1 metabolism of ethanol and unsaturated fatty acids.

Alcohol Drinking↗

PubMed1999

Subareolar versus peritumoral injection for location of the sentinel lymph node.

BACKGROUND: Sentinel lymph node (SLN) biopsy is fast becoming the standard for testing lymph node involvement in many institutions. However, questions remain as to the best method of injection. The authors hypothesized that a subareolar injection of material would drain to the same lymph node as a peritumoral injection, regardless of the location of the tumor. METHODS: To test this theory, 68 patients with 69 operable invasive breast carcinomas and clinically node-negative disease were enrolled in this single-institution Institutional Review Board-approved trial. Patients were injected with 1.0 mCi of technetium-99 sulfur colloid (unfiltered) in the subareolar area of the tumor-bearing breast. Each patient received an injection of 2 to 5 cc of isosulfan blue around the tumor. Radioactive SLNs were identified using a hand-held gamma detector probe. RESULTS: The average age of patients entered into this trial was 55.2 +/- 13.4 years. The average size of the tumors was 1.48 +/- 1.0 cm. Thirty-two percent of the patients had undergone previous excisional breast biopsies. Of the 69 lesions, 62 (89.9%) had SLNs located with the blue dye and 65 (94.2%) with the technetium. In four patients, the SLN was not located with either method. All blue SLNs were also radioactive. All located SLNs were in the axilla. Of the 62 patients in which the SLNs were located with both methods, an average of 1.5 +/- 0.7 SLNs were found per patient, of which 23.2% had metastatic disease. All four patients in which no SLN was located with either method had undergone prior excisional biopsies. CONCLUSIONS: The results of this study suggest that subareolar injection of technetium is as accurate as peritumoral injection of blue dye. Central injection is easy and avoids the necessity for image-guided injection of nonpalpable breast lesions. Finally, subareolar injection of technetium avoids the problem of overlap of the radioactive zone of diffusion of the injection site with the radioactive sentinel lymph node, particularly in medial and upper outer quadrant lesions.

Adult↗

PubMed1998

Urine cytology of primary and secondary urinary bladder adenocarcinoma.

BACKGROUND: Primary and secondary adenocarcinomas of the urinary bladder are uncommon, and the urine cytology of these tumors has rarely been described. Familiarity with the cytomorphology of these neoplasms may facilitate their detection in urine cytology specimens. METHODS: The authors reviewed 46 urine samples (19 voided, 19 instrumented, and 8 bladder washings) from 41 patients with biopsy-proven primary urinary bladder adenocarcinoma (n = 11) or metastatic adenocarcinoma (n = 35) from the prostate (n = 17), colon (n = 10), breast (n = 3), kidney (n = 3), or uterus (n = 1), or from unknown origin (n = 1). Cytomorphology, the role of cytology, and causes for negative diagnoses were evaluated. RESULTS: Cytologic diagnoses of malignancy, adenocarcinoma not otherwise specified, and adenocarcinoma of a specific type were given in 87%, 28%, and 39% of cases, respectively. Columnar cells, coarse chromatin, and necrosis were found in adenocarcinoma of the colon. Syncytial and acinar arrangements, round or oval nuclei, vesicular chromatin, and prominent nucleoli were commonly found in adenocarcinoma of the prostate. These features permitted us to make a specific diagnosis in 90% of cases of adenocarcinoma of the colon and 41% of cases of adenocarcinoma of the prostate. Cytologic examination failed to lead to a diagnosis of malignancy in 18% of primary adenocarcinoma cases. CONCLUSIONS: A large number of adenocarcinomas of the colon and prostate have sufficient cytologic features to suggest the correct diagnosis in urine samples. The cytomorphology of primary bladder adenocarcinoma is not as easily characterized. The submucosal nature of some metastatic deposits and tumor differentiation influence the diagnostic accuracy.

Adenocarcinoma↗

PubMed1998

Carcinoid tumor metastatic to the breast.

Breast metastases from nonmammary malignant neoplasms are uncommon, accounting for approximately 2% of breast tumors. There are 13 cases reported in the literature of carcinoid tumor metastatic to the breast, and more than half of these cases were misdiagnosed pathologically and treated as primary breast carcinoma, even in cases with a medical record of carcinoid tumor. We describe a patient with a history of asthma and diarrhea who presented to the University of Arkansas for Medical Sciences, Little Rock, with an exacerbation of the asthma. The results of routine physical examination revealed a mass in the left breast. A diagnosis of carcinoid tumor metastatic to the breast was made after a partial mastectomy was performed. The differential diagnosis between primary carcinoid tumor of the breast and carcinoid tumor metastatic to the breast is often controversial in surgical pathology. Diagnoses need to be made correlating clinical and histological examination in difficult cases in which there is not a diagnosis of carcinoid tumor elsewhere. Accurate diagnosis of breast metastases is important to avoid unnecessary treatment.

Aged↗

PubMed1998

Use of touch preps for intraoperative diagnosis of sentinel lymph node metastases in breast cancer.

BACKGROUND: Intraoperative touch prep (TP) is highly accurate for determining positive breast cancer margins and thereby reducing the need for second surgeries. It also may be useful in determining the status of the sentinel lymph node (SLN) during the initial surgical resection. The objective of this study was to test the ability of intraoperative TP to predict metastatic disease and, thus, the necessity for axillary lymph node dissection (ALND) at the time of SLN biopsy. METHODS: Fifty-five patients with invasive breast cancer were entered in the SLN biopsy protocol. The SLN was identified by gamma probe, dissected, and sent to pathology for TP and permanent sections. Level I and II ALND was then performed. Any radiolabeled LN in the lymphadenectomy specimen also was sent for TP and permanent sections. RESULTS: A total of 124 radiolabeled lymph nodes (LNs) were submitted for TP; of these, 93 (75%) were SLNs. Pathologic diagnosis by TP was correct compared with permanent sections for 99.2% of the nodes. There were no false positives. There was one (0.8%) false negative. The positive predictive value was 100% and the negative predictive value was 99%. Sensitivity was 95.7% and specificity was 100%. CONCLUSIONS: TP is a simple, quick, and accurate method for detecting metastatic disease in the SLN and, when used intraoperatively, enables the surgeon to determine whether or not an ALND is necessary at the time of the initial surgery.

Adult↗