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ABSTRACT: The DNA methylation mediated by specific DNA methyltransferases (DNMTs), results in the epigenetic silencing of multiple genes which are implicated in human breast cancer. We hypothesized that the natural compounds modulate the expression of DNMTs and their associated proteins in the breast cancer cell lines and affect the methylation mediated gene silencing.
The DNMTs transcript expression was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) in the tumors and the adjacent normal breast tissues of the patients with invasive ductal breast carcinoma. We tested the hypothesis that the natural compounds, viz., epigallocatechin gallate (EGCG), genistein, withaferin A, curcumin, resveratrol, and guggulsterone, have demethylation potential. To investigate this hypothesis, we analyzed the DNMTs expression at the transcript levels, followed by the analysis of DNMT1 and its associated proteins (HDAC1, MeCP2, and MBD2).
The increased DNMTs transcripts expression, viz., DNMT1, DNMT3a, and DNMT3b, in the breast cancer tissues suggest involvement of the DNMTs in the breast carcinogenesis. Quantitative RT-PCR analysis revealed that the treatment with natural compounds, viz., EGCG, genistein, withaferin A, curcumin, resveratrol, and guggulsterone, resulted in a significant decrease in the transcript levels of all the DNMTs investigated. Importantly, these natural compounds decreased the protein levels of DNMT1, HDAC1, and MeCP2.
Our results demonstrate that the natural compounds, EGCG, genistein, withaferin A, curcumin, resveratrol, and guggulsterone, have the potential to reverse the epigenetic changes. Moreover, their lack of toxicity makes these natural compounds promising candidates for the chemoprevention of the breast cancer. In-depth future mechanistic studies aimed to elucidate how these compounds affect the gene transcription are warranted.
Journal of Breast Cancer 03/2013; 16(1):23-31. · 0.32 Impact Factor
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ABSTRACT: Congenital agenesis of the parotid gland is rare, and its association with accessory parotid tissue is even rarer. We report an unusual case of unilateral agenesis of the left parotid gland associated with pleomorphic adenoma of the left accessory parotid gland. To best of our knowledge, this is only the second such published case in the literature.
Ear, nose, & throat journal 01/2013; 92(1):E13-5. · 0.66 Impact Factor
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ABSTRACT: Identification of biomarkers for monitoring efficacy of neoadjuvant chemotherapy in breast cancer patients is of utmost importance in individual tailoring of treatment and save from toxicity due to non-effective drugs. We hypothesized that methylation of circulating tumor-specific DNA may reflect changes in tumor burden in response to chemotherapy and help stratify responders from non-responders. The aim of this study was to evaluate the potential of methylation changes in circulating DNA to monitor treatment response of breast cancer patients. Six consecutive sera samples collected from 30 breast cancer patients undergoing neoadjuvant chemotherapy were analyzed for methylation status of a panel of five genes namely, BRCA1, MGMT, GSTP1, Stratifin, and MDR1. Among these five genes, BRCA1 methylation frequency was different among responders and non-responders groups. The correlation coefficients between total gene methylation with initial chemotherapy and tumor volume reduction were R (2) = 0.8 and R (2) = 0.05 in the responders and non-responders groups, respectively. Our findings warrant further development of this approach for monitoring response in patients undergoing neoadjuvant chemotherapy.
Tumor Biology 06/2012; · 1.94 Impact Factor
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ABSTRACT: To determine concordance of promoter hypermethylation of ERβ (estrogen receptor β) and RARβ2 (retinoic acid receptor β2) in tumor and circulating DNA of Indian breast cancer patients and their association with clinicopathologic parameters and disease prognosis.
ERβ and RARβ2 methylation was analyzed by methylation-specific PCR in the tumors and circulating DNA of 100 patients with invasive ductal breast carcinoma. Promoter hypermethylation was associated with the expression of the encoded protein in tumors by immunohistochemistry, and their prognostic utility was explored in a follow-up study.
Significant correlation was observed between promoter hypermethylation of ERβ (r = + 0.77; p ≤ 0.001) and RARβ2 (r = + 0.85; p ≤ 0.001) in tumors and paired sera. No association was found between ERβ and RARβ2 promoter hypermethylation and loss of protein expression. Kaplan-Meier survival curve showed loss of ERβ expression, and RARβ2 promoter hypermethylation was associated with poor overall survival (OS) (p = 0.03, p = 0.001). Breast cancer patients showing concurrent hypermethylation of ERβ and RARβ2 had a significantly shorter median OS (p = 0.02), underscoring that hypermethylation of these two genes may serve as an adverse prognosticator for breast carcinoma.
Methylation status of ERβ and RARβ2 in serum could potentially be used to predict invasive ductal breast carcinoma. Furthermore, concurrent ERβ and RARβ2 methylation as well as loss of ERβ expression may serve as a good prognostic marker.
Annals of Surgical Oncology 03/2012; 19(9):3107-15. · 4.17 Impact Factor
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ABSTRACT: We carried out retrospective analysis of apparent diffusion coefficient (ADC) values in 48 infiltrating ductal breast cancer patients who had dynamic contrast-enhanced magnetic resonance imaging (DCEMRI; Group I) and in 53 patients (Group II) for whom DCEMRI data were not available. Twenty-three patients of Group I showed no necrosis (Group Ia), while in 25 patients, both viable (nonnecrotic) and necrotic tumor areas (Group Ib) were observed on DCEMRI. T1-weighted, fat-suppressed and short inversion recovery images were used to identify the viable and necrotic tumor areas in Group II patients, and necrosis was not seen in 11 patients (Group IIa), while 42 (Group IIb) showed both viable and necrotic tumor areas. The ADCs of the necrotic area of Group Ib (1.79±0.30 ×10(-3) mm(2)/s) and Group IIb (1.83±0.40 ×10(-3) mm(2)/s) patients were similar and significantly higher (P<.01) compared to the ADCs of the viable tumor area of Group Ia (0.96±0.21 ×10(-3) mm(2)/s) and Group IIa (0.90±0.17 ×10(-3) mm(2)/s) patients. Proton MR spectroscopy (MRS) data were also available in these patients, and the ADC values were retrospectively determined from the voxel from which MR spectrum was obtained. These values were compared with the ADC obtained for the viable and necrotic areas of the tumor. ADC of the MRS voxel was similar to that obtained for the viable tumor area in patients of both groups. This interesting observation reveals the potential utility of using ADC values to identify viable tumor area for positioning of voxel for MRS in the absence of DCEMRI data.
Magnetic Resonance Imaging 03/2012; 30(5):649-55. · 1.99 Impact Factor
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ABSTRACT: The association of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) status of breast cancer patients with total choline (tCho) concentration and tumor volume was investigated using in vivo proton magnetic resonance spectroscopy and MRI at 1.5 T. Values for tCho concentration were determined in 120 locally advanced breast cancer patients (stages IIB, IIIA, IIIB, and IIIC), 31 early breast cancer patients (stage IIA), 38 patients with benign lesions, and 37 controls. Significantly higher tCho concentration and lower tumor volume were observed in early breast cancer patients compared to locally advanced breast cancer patients (P < 0.05). tCho concentration and tumor volume did not correlate with age and menstruation. tCho cutoff values were obtained for the differentiation of malignant from benign breast tissues (2.54 mmol/kg); malignant versus normal (1.45 mmol/kg) and benign versus normal tissues (0.82 mmol/kg). Estrogen receptor negative patients showed significantly larger tumor volumes, indicating higher angiogenesis with aggressive tumor behavior. Nontriple negative and triple positive patients had a significantly higher tCho concentration compared to triple negative patients (P < 0.05), indicating complex molecular mechanism of cell proliferation and the molecular heterogeneity of breast lesions. The results indicate the potential use of integration of breast (1) H magnetic resonance spectroscopy in diagnostic workup. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.
Magnetic Resonance in Medicine 12/2011; 68(4):1039-47. · 2.96 Impact Factor
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ABSTRACT: The high concentration of prostaglandins has been associated with chronic inflammatory diseases and several types of human cancers. This is due to the over expression of inflammatory enzymes like Cyclooxygenase (COX), Lipoxygenase (LOX) etc. The aim of this study was to quantify the LOX-12 with clinicopathological parameter of breast cancer patients and its response after chemotherapy to establish serum LOX-12 as a prognostic marker. This case-controlled study was performed on 86 biopsy proven breast cancer patients. Blood and tissue samples were collected from the patients. Serum LOX-12 of the study group was quantified by Surface Plasmon Resonance (SPR) and ELISA techniques by antibody-antigen interaction strategy. A significant increase in LOX-12 levels was observed in breast cancer patients (Mean ± SD=40.54±13.61 ng/ml) as compared to healthy controls (Mean ± SD=13.42±2.4 ng/ml) (p<0.0001). Serum LOX-12 levels were significantly higher (p<0.002) in patients with lymph node involvement. More than 75% patients had shown significant (p<0.0001) reduction of LOX-12 levels after chemotherapy. This was also confirmed by ELISA. This study for the first time had co-related the quantity of serum LOX-12 with breast cancer and also with the effect of chemotherapy.
Biochemical and Biophysical Research Communications 09/2011; 414(2):304-8. · 2.48 Impact Factor
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ABSTRACT: Herniation of bladder in inguinal hernia is rare, with most cases diagnosed intraoperatively. Preoperative diagnosis is even rarer. We report a case of bladder as content of inguinal hernia diagnosed using multidetector computed tomography.
Indian Journal of Urology 07/2011; 27(3):413-4.
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ABSTRACT: Cyclooxygenase-2 (COX-2), an inducible enzyme, has been implicated in the progression and angiogenesis of breast cancer. The aim of the study is to quantify the concentration of COX-2 and its association with clinico-pathological parameters and response to treatment in patients with invasive ductal carcinoma receiving both neo-adjuvant and adjuvant chemotherapy. The level of COX-2 was estimated using a novel biosensor-based surface plasmon resonance technique in serum of 84 patients with breast cancer (48 patients of neo-adjuvant chemotherapy and 36 patients of adjuvant chemotherapy) and 40 age- and gender-matched normal individuals. A significant increase in COX-2 level was observed in patients compared with normal individuals (p > 0.0001). The COX-2 level in serum was found to be significantly higher in patients with lymph node involvement (p < 0.0061). 68% (33/48) of the patients receiving neo-adjuvant chemotherapy showed significantly (p < 0.0025) reduced COX-2 levels. This study shows significant decrease of COX-2 level in patients with breast cancer treated with both neo-adjuvant and adjuvant chemotherapy. Estimation of COX-2 level in serum may serve as a tumor biomarker in patients with breast cancer.
DNA and cell biology 04/2011; · 2.28 Impact Factor
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ABSTRACT: Maspin is a serine protease inhibitor with tumor-suppressor activity. Maspin can suppress tumor growth and metastasis in vivo and tumor cell motility and invasion in vitro. Previous studies indicate that the loss of Maspin expression is closely linked to aberrant methylation of the Maspin promoter. We examined the promoter methylation status of Maspin in tumor and corresponding serum of breast cancer patients. In addition, protein expression of this gene was also assessed to determine possible correlation between promoter hypermethylation and gene silencing. Further, we investigated the correlation of Maspin expression with vascular endothelial growth factor (VEGF-A) and MTA1 expression. Maspin methylation was analyzed by methylation-specific PCR in 100 invasive ductal breast carcinoma patients' tumors and circulating DNA in a prospective study. Promoter hypermethylation was correlated with expression of the encoded protein in tumors by immunohistochemistry. Significant correlation was observed between promoter hypermethylation of Maspin (r = +0.88; p ≤ 0.0001) in tumors and paired sera. Significant association was found between Maspin promoter hypermethylation and loss of its protein expression (p = 0.01, OR = 3.1, 95% CI = 1.3-7.4). The expression of VEGF-A and MTA1 was lower in tumors with high Maspin expression compared to tumors with loss of Maspin expression. Our results indicate that aberrant promoter methylation is associated with loss of Maspin immunoreactivity in breast cancer tissues. Further, loss of Maspin expression is significantly correlated with increased expression of VEGF-A and MTA1.
Tumor Biology 02/2011; 32(1):23-32. · 1.94 Impact Factor
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ABSTRACT: The aim of our study was to evaluate whether blood flow in locally advanced and inflammatory breast cancer before and after neoadjuvant chemotherapy using color Doppler ultrasonography can be used to monitor the response to therapy and identify possible correlations between survival and various Doppler indices. Fifty patients with breast cancer underwent Doppler evaluation of the tumor with determination of Doppler indices such as pulsatility index (PI), resistive index (RI), and peak systolic velocity (PSV). RI and PI decreased in 27 (54%) and 20 (40%) patients, respectively, and increased in 23 (46%) and 30 (60%) patients, respectively. Thirty (60%) patients showed a decrease in PSV and 20 (40%) patients an increase. Patients with an intratumoral blood flow velocity increase after chemotherapy had a greater likelihood of local recurrence and metastasis compared with patients in whom flow velocity decreased after chemotherapy. The study also confirmed a greater correlation between Doppler PSV and clinical assessment. Tumor flow velocity measured by Doppler ultrasound can be used as an independent marker of disease-free survival in patients with breast cancer.
European journal of radiology 08/2010; 75(2):e158-62. · 2.65 Impact Factor
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ABSTRACT: Deep vein thrombosis [DVT] is one of the most dreaded complications in post-operative patients as it is associated with considerable morbidity and mortality. Majority of patients with postoperative DVT are asymptomatic. The pulmonary embolism, which is seen in 10% of the cases with proximal DVT, may be fatal. Therefore it becomes imperative to prevent DVT rather than to diagnose and treat. Only one randomized trial has been reported from India to assess the effectiveness of low molecular weight heparin in preventing post-operative DVT. To assess the risk of DVT in North Indian patients following major abdominal operations and to evaluate the effectiveness of Nadroparin, A Low Molecular Weight Heparin (LMWH) therapy in preventing post-operative DVT. Sixty five patients were randomised preoperatively into Group-I; Nadroparin prophylaxis and Group-II: No prophylaxis. The primary outcome was the occurrence of DVT, diagnosed by bilateral lower limb venogram performed, seven to ten days after operation. Secondary outcome measures included adverse effects of radio-opaque dye, intra-operative blood loss, operating time, postoperative platelet count, intraoperative blood transfusion requirements and the total duration of postoperative bed rest. No case of DVT occurred in either group. There was no statistical difference in the risk of secondary outcome measures in the two groups. DVT was not observed in any of the patients, even with several high risk factors indicating a possible protective mechanism in the North Indian population.
Indian Journal of Surgery 08/2010; 72(4):312-7. · 0.08 Impact Factor
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ABSTRACT: The clinical relevance of frequent methylation of CpG islands of key cancer genes in breast cancer is being increasingly recognized. Our study aimed to evaluate the promoter methylation status of DNA repair genes-BRCA1MGMT and GSTP1 in tumor and circulating DNA of invasive ductal breast carcinoma patients.
Methylation-specific PCR was carried out to investigate the promoter methylation status of genes in tumor and circulating DNA of 100 breast cancer patients in a prospective study. The effect of promoter methylation on protein expression was evaluated by immunohistochemistry.
The frequency of tumor hypermethylation was 27% in BRCA1, 32% in MGMT and 25% in GSTP1 and correlated with methylation of these genes in paired serum DNA. Immunohistochemical analysis showed no detectable expression of BRCA1 and MGMT in 51/89 (57%) and 35/89 (39%) tumors, respectively. MGMT promoter methylation mediated gene silencing was associated with loss of its protein expression (p=0.002, O.R.=4.5, 95% C.I.=1.7-12.0). BRCA1 promoter methylation was not associated with loss of its protein expression, indicating that methylation is not the sole mechanism accounting for the loss/reduced BRCA1 protein expression. Importantly, GSTP1 and BRCA1 hypermethylation were found to be independent of other prognostic factors in predicting disease recurrence (p=0.02, HR=7.6, 95% C.I.=1.4-44.1; p=0.04, HR=6.2, 95% C.I.=1.1-35.7).
Our study underscores the potential utility of DNA methylation of these genes in serum as a promising biomarker and can serve as a surrogate for tumor DNA methylation for diagnosis and prognosis of breast cancer.
Life sciences 07/2010; 87(3-4):83-91. · 2.56 Impact Factor
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Indian Journal of Gastroenterology 07/2010; 29(4):171.
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ABSTRACT: Breast cancer is the most common cancer in Indian women. The aim of this study was to assess the levels of red blood cell (RBC) superoxide dismutase (r-SOD), RBC catalase (r-CAT), RBC glutathione peroxidase (r-GPx) and the ferric reducing ability of plasma (FRAP) in advanced breast cancer patients post mastectomy before and after chemotherapy.
Female breast cancer patients between 27 and 65 years of age who were admitted to the Department of Surgery of the All India Institute of Medical Sciences in New Delhi were enrolled in the study. This study included two arms: a control group of healthy age-matched females (n=20) and patients undergoing treatment with a combination of the anticancer drugs cyclophosphamide, doxorubicin, and 5-fluorouracil (CAF) (n=55), No treatment was given to the control group. The CAF group received CAF treatment at weeks 0, 3, and 6, then surgery at week 9 followed by CAF treatment at weeks 12, 15, and 18. A three-week drug-free interval was included between each cycle of drug treatment. Blood samples were collected from control subjects and from patients in the CAF group before administration of drugs at week zero to establish a baseline, again weeks 12 and 18, and once more at the end of the 26-week treatment. Blood samples collected from the control subjects and CAF patients were analysed to determine levels of the endogenous antioxidants, r-SOD, r-CAT, r-GPx, and FRAP.
Levels of r-SOD, r-CAT, r-GPx, and FRAP in CAF-treated patients at 12, 18, and 26 weeks were significantly decreased (P<0.001) in comparison to the baseline levels observed at week zero.
The results from the present study show that a change in the enzyme antioxidant systems in patients after chemotherapy and mastectomy causes an overall decrease in antioxidant levels. Chemotherapeutic agents induce oxidative stress that damages many cellular targets.
The Malaysian journal of medical sciences : MJMS. 04/2010; 17(2):24-8.
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ABSTRACT: The potential of total choline (tCho) signal-to-noise ratio (SNR) (ChoSNR) and tumor volume in the assessment of tumor response in locally advanced breast cancer (LABC) patients (n = 30) undergoing neoadjuvant chemotherapy (NACT) was investigated using magnetic resonance spectroscopic imaging (MRSI) and conventional MRI at 1.5 T. Experiments were carried out sequentially at four time-points: prior to therapy and after I, II and III NACT and ChoSNR, and the tumor volume was measured. The MR response was compared with the clinical response. Sequential data of 25 patients were retrospectively analyzed by classifying them as clinical responders and non-responders. In 14 responders, the pre-therapy ChoSNR was 7.8 +/- 5.1. In 10/14 responders, no choline was observed after III NACT while in the remaining four patients the ChoSNR was reduced to 3.6 +/- 1.1 (p < 0.05). Non-responders showed no statistically significant change in ChoSNR. After III NACT, the tumor volume reduced by 84.0 +/- 14.8% in responders. Using receiver operating curve (ROC) analysis, cut-off values of 53% for ChoSNR and 47.5% for volume were obtained to differentiate responders from non-responders. The sensitivity to detect responders from non-responders using ChoSNR was 85.7% with 91% specificity while 100% sensitivity was observed for volume but with reduced specificity of 73%. Our results indicate that ChoSNR may serve as a useful parameter to predict tumor response to NACT with higher specificity compared to volume, suggesting its potential in effective treatment management.
NMR in Biomedicine 02/2010; 23(3):233-41. · 3.21 Impact Factor
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ABSTRACT: The axillary lymph node status is the most important determinant of prognosis in patients with breast cancer. Sentinel lymph node (SLN) biopsy is a safe alternative for axillary clearance with an equal efficacy limiting the morbidity caused by axillary clearance.
From May 1996 till September 2009, 523 clinically node negative, early breast cancer patients attending our clinic at All India Institute of Medical Sciences were included in the study. They underwent sentinel lymph node biopsy by either combined technique or blue dye alone. All patients irrespective of the axillary status underwent axillary lymph node dissection (ALND).
Of 523 patients, 267 underwent combined technique of sentinel node mapping and 256 underwent blue dye technique alone. The identification rate of sentinel lymph node was 94.3% (253/267) for combined technique and 87.8% (225/256) for blue dye alone. Of 523 patients SLN was identified in 478 patients. The identification rate was 91.3%. The sensitivity = 91.5% (141/154), false negative = 8.4% (13/154), negative predictive value = 96.14% (324/337), and accuracy being 97.2% (465/478).
Sentinel node mapping is a simple and safe technique of identifying the axillary node involvement. Sentinel lymph node biopsy is associated with less arm oedema and shoulder morbidity compared to ALND. However, the results of long term effects of sentinel node approach on tumor recurrence or patient survival are awaited.
Indian journal of surgical oncology. 01/2010; 1(1):52-8.
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ABSTRACT: The objective of this study was to determine the concordance of promoter methylation of stratifin, ERalpha and PR in tumor and circulating DNA in breast cancer patients and their association with clinicopathological parameters and disease prognosis.
Methylation specific PCR were carried out to investigate the promoter methylation status of stratifin, ERalpha and PR in tumor and circulating DNA in 100 breast cancer patients in a prospective study. The effect of promoter methylation on protein expression was evaluated by immunohistochemistry.
Significant association was observed between promoter methylation of stratifin in tumors (61%) and paired sera (56%) (r=0.78; p < or = 0.001). Loss of stratifin expression was observed in 47% tumors and was associated with poor overall survival (p=0.05). Significant correlation was observed between methylation status of ERalpha with PRB (p<0.0001, OR=20.8, 95% CI=7.4-58.0) and stratifin (p=0.003, OR=2.0, 95% CI=0.8-4.4).
This study underscores the potential utility of serum DNA methylation of these genes as surrogate for tumor DNA methylation as a promising tool for cancer diagnosis.
Clinical biochemistry 12/2009; 43(4-5):380-6. · 2.02 Impact Factor
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ABSTRACT: Inflammatory conditions are the most common pathology affecting the salivary glands. Magnetic resonance (MR) sialography has emerged as an alternative to conventional sialography for evaluation of inflammatory salivary gland diseases.
To prospectively evaluate the role and diagnostic accuracy of MR sialography in the diagnosis of inflammatory salivary gland disease.
Thirty-seven glands in 28 patients (19 males and nine females; mean age 31 years, range 3-65 years) presenting with inflammatory salivary gland disorders underwent MR sialography. Conventional sialography was used as the gold standard and was performed in 26 patients (34 glands). Thus, comparative evaluation was done in 26 patients (34 glands). Axial T1-weighted (T1W) and fat-suppressed T2W sequences, a constructive interference in steady state (CISS) sequence in the axial plane with maximum intensity projection (MIP)/multiplanar reformation (MPR) done in the axial and sagittal oblique planes, and a half-Fourier acquisition single-shot turbo spin-echo (HASTE) sequence in the sagittal oblique direction were performed.
Main salivary gland duct was visualized in 32 glands (94.1%) with MR sialography, and in all 34 (100%) glands with conventional sialography. Calculus and strictures were well demonstrated by MR sialography. MR sialography was superior for demonstration of the ductal system proximal to calculus/strictures. Sensitivity and specificity for diagnosis of specific pathology were 87% and 100% with CISS sequence and 90% and 75% with HASTE sequence, respectively. On using a combination of CISS and HASTE sequences, the sensitivity, specificity, and positive and negative predictive values in the diagnosis of specific pathology were 93%, 100%, 100%, and 64%, respectively.
MR sialography using CISS and HASTE sequences is a promising technique and has the potential to replace conventional sialography in patients with inflammatory salivary gland disorders.
Acta Radiologica 11/2009; 51(2):156-63. · 1.37 Impact Factor
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ABSTRACT: Multidrug resistance 1 (MDR1) gene encodes P-glycoprotein (P-gp), a transmembrane calcium-dependent efflux pump, implicated in drug resistance. In this prospective study, methylation status of MDR1 promoter and its correlation with clinicopathological parameters were evaluated in tumor and serum of breast cancer patients.
Methylation-specific PCR was carried out to investigate the promoter methylation status of MDR1 in tumor and serum of 100 patients with invasive ductal carcinomas of breast (IDCs). The effect of promoter methylation on protein expression was evaluated by immunohistochemistry.
MDR1 was hypomethylated in 47% tumors and 44% paired sera of IDC patients and correlated significantly with increased tumor size and advanced tumor stage. Promoter hypomethylation of MDR1 in serum DNA showed 98% specificity and 50% sensitivity.
Hypomethylation of MDR1 promoter in IDCs accounted for P-gp overexpression and aggressive biologic behavior in a subset of patients. Detection of these epigenetic changes in circulating DNA may not only enhance insight into the biological behavior of the primary tumor of an individual but may also provide valuable information regarding prognosis that can be readily monitored throughout the disease course.
Clinical biochemistry 10/2009; 43(4-5):373-9. · 2.02 Impact Factor
