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Kohla et al.                                                                                                                                                                         Transforming growth factor β1 in HCC

           appropriate treatment remain the best strategy for                       180
           reducing mortality.                                                    subjects

           Transforming growth factor β (TGF-β) superfamily             Control               Cirrhotic
           is known to be involved in embryonic development,            group     CC group     group
           adult tissue homeostasis, and disease pathogenesis.          (n = 30)  (n = 120)   (n = 30)
           Specifically, it has been shown to control proliferation,
           differentiation, apoptosis, migration, extracellular matrix   BCLC 0&A   BCLC B   BCLC C  BCLC D
           remodeling, immune functions, and tumor invasion/      (n = 30)    (n = 30)   (n = 30)   (n = 30)
                     [4]
           metastasis . TGF-β enhances hepatic stellate cell
           activation, stimulates collagen gene transcription and
           suppresses matrix metalloproteinases expression.
           Thus, TGF-β, as well as its intracellular mediators;
           Smad proteins, can be potential therapeutic targets for       Serum TGF-b1 level measurement and
           liver fibrosis. TGF-β inhibits hepatocyte proliferation,           follow-up for 18 months
           but it also promotes HCC. TGF-β has been shown to
           play both tumor-suppressive at early stage and tumor-
                                      [5]
           promoting roles at later stage . At the early stage of
           tumorogenesis, TGF-β1 inhibited normal cell growth
                                                                                                      Alive
           and tumorogenesis by suppressing G1/S phase          Deceased                             (n = 118)
                                                                 (n = 62)
                    [6]
           transition , in later stages; malignant cells become
           resistant to suppressive effects of TGF-β either through   Figure 1: Flow chart of the study. BCLC: Barcelona clinic
           mutation and/or functional inactivation of TGF-β   liver cancer; TGF-b1: transforming growth factor beta 1; HCC:
                                                              hepatocellular carcinoma
           receptors or by downstream alterations in the SMAD-
                           [7]
           signaling pathway . Mutations in downstream TGF-β
           signaling components cause variable attenuations or   intermediate stage (BCLC B); group 3 comprised
           complete loss of expression; these mutations, which   30 patients with an advanced HCC stage (BCLC C);
           have been detected in many common tumors, affect   group 4 comprised 30 patients with a terminal HCC
           TGF-β signal transmission that potentially results   stage (BCLC D); group 5 comprised 30 patients
                                                         [8]
           in human cancer development and progression .      with cirrhosis without evidence of HCC; and group
           TGF-β1 expression was related to tumor grade and   6 comprised 30 healthy subjects as a control group
           pathological stage. Furthermore, overexpression of   [Figure 1].
           plasma TGF-β1 was associated with invasiveness of   The diagnosis of HCC was based on non-invasive
                                  [9]
           HCC and worse prognosis .
                                                              criteria using multi-slice triphasic spiral computed
                                                              tomography or contrast enhanced dynamic magnetic
           The aim of this study was to evaluate the association   resonance imaging. The presence of typical features
           between serum level of TGF-β1 and disease severity   of arterial enhancement and rapid portal or delayed
           in Egyptian patients with HCC.                     washout on one imaging technique was diagnostic
                                                              of HCC for nodules > 2 cm in diameter in cirrhotic
           METHODS                                            patients. In cases of uncertainty or atypical radiological
                                                              findings, diagnosis was confirmed by biopsy [10] . Liver
           This cross sectional study was conducted at National   cirrhosis was diagnosed by ultrasonographical findings
           Liver Institute, Menoufia University. The study protocol   (shrunken liver, coarse echo pattern, attenuated
           was approved by institute Ethics Committee. A written   hepatic veins and nodular surface) and biochemical
           informed consent was obtained from all participants in   indication of parenchymal harm.
           the study.
                                                              Laboratory investigations
           The study was performed on 180 subjects attending   Venous blood (10 mL) were drawn from all participants
           HCC and cirrhosis clinics, 120 HCC patients, 30    and divided into 3 parts: the 1st part, 2 mL was
           cirrhotic patients and 30 matched apparently healthy   collected in EDTA containing tube for complete blood
           subjects served as control group. HCC patients     picture using Sysmex K-21, (Sysmex Corporation,
           were classified according to Barcelona clinic liver   Kobe, Japan); the 2nd part, 5 mL for serum which
           cancer (BCLC) classification into 6 groups: group 1   was used for assessment of liver function tests using
           comprised 30 patients with an early HCC stage (BCLC   fully automated autoanalyzer SYNCHRON CX9ALX
           0 and A); group 2 comprised 30 patients with HCC   (Beckman Coulter Inc., CA, USA), for immunoassay

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