[Recognition of the membrane anatomy-based laparoscopic assisted right hemicolectomy].

Although it has become a consensus in the field of colorectal surgery to perform radical tumor treatment and functional protection under the minimally invasive concept, there exist many controversies during clinical practice, including the concept of embryonic development of abdominal organs and membrane anatomy, the principle of membrane anatomy related to right hemicolectomy, D3 resection, and identification of the inner boundary. In this paper, we analyzed recently reported literature with high-level evidence and clinical data from the author's hospital to recognize and review the membrane anatomy-based laparoscopic assisted right hemicolectomy for right colon cancer, emphasizing the importance of priority of surgical dissection planes, vascular orientation, and full understanding of the fascial space, and proposing that the surgical planes should be dissected in the parietal-prerenal fascial space, and the incision should be 1 cm from the descending and horizontal part of the duodenum. The surgery should be performed according to a standard procedure with strict quality control. To identify the resection range of D3 dissection, it is necessary to establish a clinical, imaging, and pathological evaluation model for multiple factors or to apply indocyanine green and nano-carbon lymphatic tracer intraoperatively to guide precise lymph node dissection. We expect more high-level evidence of evidence-based medicine to prove the inner boundary of laparoscopic assisted radical right colectomy and a more rigorous consensus to be established.

[Long-term outcomes of lateral vocal fold autologous fat injection for unilateral vocal fold paralysis].

Objective: To investigate the long-term outcomes of patients with unilateral vocal fold paralysis resulting in dysphonia treated with lateral vocal fold autologous fat injection. To analyze the factors that may affect the long-term efficacy of the procedure. Methods: From July 2003 to June 2020, 163 patients (86 males and 77 females), aged 9-73 years (mean (34.50±12.94) years) with unilateral vocal fold paralysis resulting in dysphonia underwent transoral laryngoscopic injection of autologous fat into the lateral vocal folds. Subjective auditory perception assessment (GRBAS scale), objective acoustic assessment, voice handicap index (VHI) evaluation and stroboscopic laryngoscopy were compared before and after the surgery. Patients were followed up for 1 to 18 years, with median follow-up time of 6 years. SPSS 22.0 software was used for statistical analysis. Results: Of 163 patients, 17 patients (10.4%) had mild hoarseness (G1) and 146 patients (89.6%) had moderate to severe hoarseness (G2-3). Stroboscopic laryngoscopy revealed an arch-shaped vocal fold on the affected side, fixed in the paramedian position or abduction position, with obvious glottic closure fissure. Postoperatively, voice recovered to normal (G0) in 139 patients (85.3%), mild hoarseness (G1) in 18 patients (11.0%) and moderate hoarseness (G2) in 6 patients (3.7%). Of these, 131 patients (80.4%) showed significant improvement in hoarseness, 29 patients (17.8%) showed mild improvement and 3 patients (1.8%) showed no significant improvement in hoarseness. Objective acoustic parameters of Jitter, Shimmer, NHR and MPT improved significantly, as did VHI scores. Stroboscopic laryngoscopy showed medialization of the affected vocal folds, improved vocal fold closure and normal or nearly normal vocal fold mucosal waves. With a fat injection volume of 3.0-4.5 ml, the patient's subjective auditory perception scores of G, R, B and A improved more significantly within 3 months after surgery, and both VHI and MPT were significantly better since 1 year after surgery. With bilateral vocal fold injection, the B and A scores improved significantly from 1 month postoperatively compared to unilateral injections(unilateral vs. bilateral injection 1 month post-operation, tB scores=1.42,tA scores=1.51,P<0.05). Conclusions: The long-term efficacy of autologous fat injection in the paraglottic space for the treatment of unilateral vocal fold paralysis was stable. The efficacy of the surgery was related to the amount of fat injected, unilateral or bilateral of the injection.

[Study on changes of voice characteristics after adenotonsillectomy or adenoidectomy in children].

Objective: To study voice changes in children after adenotonsillectomy or adenoidectomy and the relationship with the vocal tract structure. Methods: Fifty patients were recruited in this study prospectively, aged from 4 to 12 years old with the median age of 6. They were underwent adenotonsillectomy or adenoidectomy in Beijing Tongren Hospital, Capital Medical University from July 2019 to August 2020. In the cases, there are 31 males and 19 females. Thirty-six patients underwent adenotonsillectomy and 14 patients underwent adenoidectomy alone. Twenty-two children (13 males, 9 females) with Ⅰ degree of bilateral tonsils without adenoid hypertrophy and no snoring were selected as normal controls. Adenoid and tonsil sizes were evaluated. Subjective changes of voice were recorded after surgery. Moreover, voice data including fundamental frequency(F0), jitter, shimmer, noise to harmonic ratio(NHR), maximum phonation time(MPT), formant frequencies(F1-F5) and bandwidths(B1-B5) of vowel/a/and/i/were analyzed before, 3 days and 1 month after surgery respectively.SPSS 23.0 was used for statistical analysis. Results: Thirty-six patients(72.0%,36/50) complained of postoperative voice changes. The incidence was inversely correlated with age. In children aged 4-6, 7-9, and 10-12, the incidence was 83.3%(25/30), 63.6%(7/11) and 44.4%(4/9) respectively. Voice changes appeared more common in children underwent adenotonsillectomy(77.8%,28/36) than in those underwent adenoidectomy alone(57.1%,8/14), but there was no statistical difference. After operation, for vowel/a/, MPT(Z=2.18,P=0.041) and F2(t=2.13,P=0.040) increased, B2(Z=2.04,P=0.041) and B4(Z=2.00,P=0.046) decreased. For vowel/i/, F2(t=2.035,P=0.050) and F4(t=4.44,P=0.0001) increased, B2(Z=2.36,P=0.019) decreased. Other acoustic parameters were not significantly different from those before surgery. The F2(r=-0.392, P =0.032) of vowel/a/and F2(r=-0.279, P=0.048) and F4 (r=-0.401, P =0.028) of vowel/i/after adenotonsillectomy were significantly higher than those of adenoidectomy alone. Half of patients with postopertive voice changes can recover spontaneously 1 month after surgery. Conclusions: Voice changes in children underwent adenotonsillectomy or adenoidectomy might be related to their changes in formants and bandwidths. The effect of adenotonsillectomy on voice was more significant compared with that of adenoidectomy alone. The acoustic parameters did not change significantly after surgery except MPT.

[Diagnosis and endoscopic treatment of blunt laryngeal trauma with arytenoid injury].

Objective: To investigate the clinical characteristics, diagnosis, endoscopic surgical procedures, and therapeutic effect of blunt laryngeal trauma with arytenoid injury. Methods: We retrospectively reviewed 12 patients who suffered blunt laryngeal trauma with laryngeal mucosa avulsion and arytenoid region injury at the Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital from April 2007 to December 2018. Among the 12 patients, 10 were males, 2 were females, aged from 7 to 48 years old, with a median age of 21 years old. All patients were performed with transoral endoscopic laryngeal microsurgery under general anesthesia. Clinical characteristics, laryngoscopic signs, laryngeal CT, endoscopic surgical findings and procedures, and therapeutic effect were analyzed. The subjective and objective parameters of the voice quality of patients before and after surgery were compared using SPSS 22.0 statistical software by paired T test. Results: All patients had a history of obvious dysphonia immediately after trauma, accompanied by throat pain and hemoptysis without obvious dyspnea and dysphagia. Slight subcutaneous emphysema was found in 3 patients by physical examination. Laryngoscope revealed that 14 sides of vocal folds immobilized, arytenoid and/or ventricular region and posterior glottis mucosa were avulsed in 4 patients within 48 h of injury, and arytenoid cartilage was exposed in 4 sides. The arytenoid and ventricular regions were covered with thick pseudo-membrane or granulation, with abnormal structure in 8 patients with damage of more than 48 h. Intraoperative exploration revealed that there were 17 sides of arytenoid region (bilateral 5 cases, unilateral 7 cases) with varying degrees of injury. There was only limited laceration on three sides of the vocal folds. The lateral ventricular and vocal fold mucosae were avulsed vertically from the arytenoid region and arytenoid cartilage was exposed in 14 sides, among which 6 sides had abnormal arytenoid cartilage morphology and 8 sides had fracture displacement. Laryngeal CT showed irregular thickening of lateral glottis and/or supratroglottic structures in patients with vocal folds immobility, among which asymmetry of arytenoid cartilage structure on both sides in 3 cases and displacement in 2 cases were found. Restoration and microsuture of the fractured arytenoid, perichondrium and avulsion laryngeal mucosa under the direct laryngoscope were performed. The degree of dysphonia was significantly improved immediately after laryngeal microsurgery, the voice significantly improved in G, R, B, A, jitter, shimmer, NHR, and MPT three months after surgery(t=12.792, 12.792, 10.340, 3.276, 2.865, 3.781, 3.173, 3.090, respectively, P<0.05). Except for 1 patient with scar on vocal fold, all the other patients had normal laryngeal morphology and normal vocal fold movement. No laryngeal stenosis was found during the follow-up period. Conclusions: For patients with blunt laryngeal trauma, the injury of arytenoid region and arytenoid cartilage should be evaluated if there is obvious hoarseness, vocal fold immobility, avulsion of ventricular/vocal folds mucosa, or structural abnormality of arytenoid region under laryngoscopic examination. For highly suspected cases, microrphonosurgery under the direct laryngoscope should be performed as soon as possible, which can effectively reduce the occurrence of vocal fold movement disorders and laryngeal scar/stenosis, reconstruct the normal laryngeal structure, and restore the vocal function.

[Re-consideration of the construction of quality control system for enhanced recovery after surgery].

The focus on enhanced recovery after surgery (ERAS) is still the implementation of the concept at present, and remains in the stage of disordered and low-quality application because of its difficulties in operation, evaluation and repeatability. The main reason is lack of standard, feasible operation plan and process, which may lead to great heterogeneity and low quality. Therefore, It is urgent to explore and establish the quality control system of ERAS, including foundation, process, terminal and tracking quality control, so as to improve the validity, security, homogeneity and accessibility, and promote the further popularization and application. However, due to the conceptual, systematic, innovative and individual differences, the construction of ERAS standard quality control system will be faced with great difficulties and challenges. ERAS quality control platform and center can only be established gradually by hard work and a lot of researches.

[The expression characteristics and clinical significance of candidate molecular markers in vocal cord leukoplakia].

Objective: To investigate the expression of marker proteins in vocal cord leukoplakia, and to find markers for the early stage of diagnosis and prognosis of precancerous lesions. Methods: The study included 119 cases, 68 cases of vocal cord leukoplakia (22 cases with epithelial simple hyperplasia, 46 cases with epithelial dysplasia), and 51 cases of vocal cords benign lesions(31 cases of vocal cord polyps, 20 cases of Reinke's edema). The expression of p53, Ki-67, p21, Survivin, p16, p27, PTEN, c-Myc and vascular endothelial growth factor (VEGF) in vocal cords leukoplakia were detected, vocal cord benign lesions (vocal cord polyps and Reinke's edema) acted as controls, comparing the expression differences of different pathological tissue. Data was analyzed by SPSS 22.0 software. Results: The expression of p53, p16, Ki-67, VEGF in vocal cord benign lesions and vocal cords leukoplakia with epithelial simple hyperplasia did not show significant differences. There was a grading increase in the positive expression of p53, Ki-67 in the vocal cord leukoplakia with epithelial dysplasia contrasting to those in vocal cord benign lesions and vocal cords leukoplakia with epithelial simple hyperplasia (p53: χ(2)=13.340, P=0.002, Ki-67: χ(2)=53.386, P=0.000). The expression of p27, PTEN, c-Myc in vocal cord benign lesions and vocal cords leukoplakia with epithelial dysplasia did not show significant differences. There was a grading increase in the positive expression of p21 Survivin in vocal cords leukoplakia with epithelial dysplasia contrasting to those in vocal cord benign lesions (P<0.05). Expression of Survivin in vocal cords leukoplakia with mild-moderate epithelial dysplasia showed a significant increase than those in vocal cord benign lesions (P<0.05). The positive expression grade of p21 showed a rising trend (P=0.073) between the different grades of dysplasia. Conclusion: The positive expression grade of p53, Ki-67, p21 Survivin showed an increase in vocal cords leukoplakia with epithelial dysplasia contrasting to those in vocal cord benign lesions, which might be an implication for evaluating the diagnosis and prognosis of precancerous lesions. Expression of p21 was correlated to the degrees of dysplasia and expression of Survivin showed a significant difference in early stage of epithelial dysplasia contrasting to benign lesions.

[Application of stroboscopy and narrow band imaging endoscopy in the diagnosis of vocal cord leukoplakia].

Objective: To investigate the value of stroboscopy and narrow band imaging (NBI)endoscopy in the diagnosis of vocal cord leukoplakia. Methods: Two hundred and forty-six patients with vocal cord leukoplakia who underwent laryngeal microsurgery and diagnosed by histopathology were recruited between August 2014 and July 2016 in this retrospective study. The diagnostic accuracy of stroboscopy and narrow band imaging endoscopy in the diagnosis of vocal cord leukoplakia was compared. SPSS21.0 software was used to analyze the data. Results: A significantly positive correlation was found between the decrease grade of mucosal wave and the histopathological diagnosis(Spearman r=0.526, P<0.01). A significantly positive correlation was found between the lesion classified by detailed morphologic findings of epithelial microvessel and the histopathological diagnosis(Spearman r=0.480, P<0.01). The sensitivity of stroboscopy for detecting severe dysplasia, carcinoma and invasive carcinoma was 92.73%, higher than NBI endoscopy. The specificity of NBI endoscopy was 90.55%, higher than stroboscopy. The results of logistic regression analysis showed: the positive pathological type risk in the group with mucosal waves severely reduced and absent was 3.906 and 19.737 times higher than the group with mucosal waves slightly reduced. In the group with mucosal waves severely reduced and absent, significant difference was observed when combined use of NBI endoscopy(P<0.001, P=0.047). Conclusions: In the diagnosis of vocal cord leukoplakia, stroboscopy is useful for detecting severe dysplasia, carcinoma and invasive carcinoma with high sensitivity. In the group with mucosal waves severely reduced and absent, combined use of NBI endoscopy was able to improve the diagnostic accuracy.

[Fifth Chinese national consensus report on the management of Helicobacter pylori infection].

The fifth national consensus conference on the management of Helicobacter pylori (H.pylori) infection organized by Chinese Medical Association, Chinese Society of Gastroenterology, H. pylori and Peptic Ulcer Study Group was held at Hangzhou, Zhejiang Province on December 15-16, 2016.More than 80 members of the study group and experts in the field of H. pylori research and gastroenterology attended the meeting.Consensus preparatory group was established to draft the related statements.The quality of evidence and strength of recommendation were evaluated by GRADE system.The Delphi method using an anonymous electronic system was adopted to develop the consensus of relevant statements.Expert advices about the established statements were firstly consulted through the emails.After two rounds of consultation, the preliminary statements of consensus were discussed and modified in the conference item by item.A total of 21 core members voted for the final version, which contained a total of 48 statements and was divided into 6 parts, including indications for H. pylori eradication, diagnosis, treatment, H. pylori and gastric cancer, H. pylori infection in special populations, H. pylori and gastrointestinal microbiota.

[Clinical and pathological characteristics of vocal fold leukoplakia and influential factors of recurrence and malignancy].

Objective:To investigate the clinical and pathological characteristics of vocal fold leukoplakia and influential factors of recurrence and malignancy. Method:The study included 555 cases of vocal fold leukoplakia. All patients received surgical treatment. The relationship between the clinical and pathological features, and influential factors of recurrence and malignancy were analyzed. Result:The pathological types included squamous epithelial simple hyperplasia in 58.0%, mild hyperplasia in 15.5%, moderate hyperplasia in 10.1%, severe hyperplasia and carcinoma in situ in 8.1%, infiltrative carcinoma in 8.3%. The different pathological types varied among different ages significantly(P<0.01). The tobacco and alcohol abuse had no relationship with pathological types(P>0.05). The more severe the pathology were, the more decreasing of the mucosal waves would be(P<0.01). The pathologic severity had an apparent correlation with p53 positivity and the level of p53 and Ki67 positivity. The p53 positive proportion may increase with the increasing pathological severity(P<0.01), so were the p53 and Ki67 positive levels(P<0.01).Among 232 cases of postoperation follow-ups, 83 cases(35.8%) relapsed while 8 cases(3.4%) malignancy. Bilateral lesions had a higher rate of relapse and malignancy than unilateral lesions(95%CIOR 0.378 ［0.197-0.723］，P<0.01). The relapse and malignancy had a relationship with the pathologic severity. The incidence of disease recurrence and malignancy were positively correlated with pathological severity(P<0.05). p16 positive patients relapsed for more times(P<0.01) and with an uprising tendency of relapse and malignancy（P>0.05）. Conclusion:Pathological types of vocal fold leukoplakia are different. The older men, decreasing of mucosal wave of vocal folds and bilateral lesions were very important factors to predict disease severity. p53 and Ki67 positive rating and pathological severity were positively correlated. The bilateral lesions, pathological severity and p16 positivity had a tendency to increasing relapse and malignancy.

Inhibitor of apoptosis proteins and ovarian dysfunction in galactosemic rats.

Galactosemia is a genetic disease with deficiency of galactose-1-uridyltransferase, resulting in the accumulation of galactose or galactose-1-phosphate in the blood and tissues. Rats were fed with normal rat chow and with a high-galactose diet for 4 weeks to give control and galactosemic groups, and their ovarian function was studied. The two groups of rats were injected with pregnant mare's serum gonadotrophin (PMSG) and were killed at different time points after human chorionic gonadotrophin (hCG) injection. The number of oocytes ovulated in the controls was significantly higher than in the galactosemic group. Morphometric studies of the ovaries also showed a higher number of corpora lutea in the controls. Western blot analysis of granulosa cells showed that the overall expressions of Fas and FasL were lower in the control group and their expressions of inhibitor of apoptosis proteins (IAPs) were higher than in the galactosemic group, especially at 8 h post hCG injection. TDT-mediated dUTP-biotin nick end-labeling (TUNEL) and immunohistochemical staining of ovarian sections with Ki-67 and IAPs showed more apoptotic granulosa cells in the galactosemic group and the expressions of IAPs in granulosa cells also confirmed the result of the Western blot. These findings support our hypothesis that ovarian dysfunction in galactosemic rats is due to increased apoptosis in granulosa cells of maturing follicles.

The outcome of shunted hydrocephalic children.

BACKGROUND: Neurological sequelae and mental retardation may result from different etiological types of hydrocephalus. The aim of our study is to determine the intellectual development and the "shunt history" of these children with regard to the complications and revision rates. METHODS: We reviewed the medical history of non-tumoral pediatric hydrocephalic patients who had received first shunt insertions between 1983 and 1997 and had been regularly followed up at the out-patient clinics of Taipei Veterans General Hospital. These patients were categorized into five different etiological groups. Their intelligence test scores and the surgical morbidity encountered over this period were used as the main outcome measures. RESULTS: Out of the seventy-three patients, post-meningitis hydrocephalus patients had the significantly highest shunt revision rate (2.50 +/- 0.82, p = 0.01). They also showed retardation in IQ scores, but the different was not significant when compared with other groups. The results of IQ tests were not related to either the age of initial shunt insertion (p = 0.461) or revision rates (p = 0.292). For physical disabilities, post-meningitis hydrocephalic patients showed-highest incidence of epilepsy (40%) while hydrocephalic patients associated with myelomeningocele had the highest incidence of motor deficits (56.25%). CONCLUSIONS: Childhood hydrocephalic patients had different developmental neuroimpairments with respect to different etiologies. This study provides information about the physical and mental outcome of post-operative hydrocephalic patients which is valuable to assist in counsel of their families.

Butein, a specific protein tyrosine kinase inhibitor.

Butein, a plant polyphenol, was shown to be a specific protein tyrosine kinase inhibitor. This compound inhibited not only the epidermal growth factor (EGF)-stimulated auto-phosphotyrosine level of EGF receptor in HepG2 cells but also tyrosine-specific protein kinase activities of EGF receptor (IC50 = 65 microM) and p60c-src (IC50 = 65 microM) in vitro. The inhibition was competitive to ATP and non-competitive to the phosphate acceptor, poly (Glu, Ala, Tyr) 6:3:1 for EGF receptor tyrosine kinase. In contrast, butein non-significantly inhibited the activities of serine- and threonine-specific protein kinases, such as protein kinase C (PKC) and cAMP-dependent protein kinase (PKA).

The thermal activity of normal and malignant tissues. Microcalorimetric response of liver cancer to hepatic artery ligation, cryosurgery, adriamycin and norcantharidin.

The usefulness of metabolic heat measurements in quantifying the response of a solid tumour to anticancer treatment was evaluated. The heat production characteristic of malignant tissues, as measured from human stomach, breast and liver cancer samples, was observed to be inconsistent, and its value could be higher or lower than that of its normal tissue of origin. The various thermal activity responses of an experimental rat hepatoma to hepatic artery ligation, cryotherapy, intra-arterial (i.a.) Adriamycin (2.4 mg/kg), i.a. Norcantharidin (0.5 mg/kg) were next studied. The tumour/liver (T/L) ratio of untreated tumour-bearing rats was 0.83 but this fell to a minimum at 24 h in both the hepatic artery ligation and the cryosurgery groups. In these two groups marked fluctuations in the heat production of normal liver occurred with poor recovery of the T/L ratio even at 2-3 weeks. In the Adriamycin group, the T/L ratio dropped to a minimum at 5 days, and in the Norcantharidin group, at 3 days. Minimal disturbances in the thermal activity of liver tissue occurred in these two chemotherapy groups and the T/L ratio recovered by 3 weeks. Norcantharidin appeared as efficacious as Adriamycin in the treatment of hepatoma when evaluated in terms of thermal activity.

Norcantharidin inhibits growth of human HepG2 cell-transplanted tumor in nude mice and prolongs host survival.

In this study, norcantharidin was compared with adriamycin and mitomycin C for its inhibitory action in the growth of cultured human hepatocellular carcinoma HepG2 cells. The IC50 of adriamycin and mitomycin C on HepG2 cells was 7.3 microM and 27 microM, respectively, whereas the IC50 of norcantharidin for inhibiting the growth of HepG2 cells was as high as 1900 microM. After HepG2 tumor-bearing nude mice were treated with 12 daily intraperitoneal injections of norcantharidin (2 mg/kg), the increase in tumor size was significantly slower than that of untreated controls. The mean survival time of untreated tumor-bearing nude mice was 129 days, whereas in the tumor-bearing nude mice treated with norcantharidin, the mean survival time was significantly prolonged to 194 days (P < 0.0001). It is concluded that norcantharidin may have a potential role in the treatment of human hepatocellular carcinoma.

Transmodulation of EGF receptor by interferon-gamma in human hepatocellular carcinoma HepG2 cells.

EGF receptor has been recognized to playing an important role in the regulation of normal and tumor cell growth. In this study, the transmodulatory effect of IFN gamma on EGF receptor of human hepatocellular carcinoma cell line HepG2 was investigated. The results demonstrated that IFN gamma was able to modulate EGF receptor of HepG2 cells by enhancing the tyrosine phosphorylation of the receptor. However, the effect appeared only if EGF was present, but not mediated by IFN gamma alone. No significant alteration was found in terms of the expression or the affinity of EGF receptor when HepG2 cells were treated with IFN gamma. In addition, EGF internalization in the cells was also not affected. Because IFN gamma is an inhibitory agent for the growth of HepG2 cells, this transmodulatory effect of IFN gamma on the tyrosine phosphorylation of EGF receptor might be associated with the inhibition of the growth of HepG2 cells.

Neuropsychological sequelae after treatment for medulloblastoma in childhood--the Taiwan experience.

The purpose of this study was to investigate the functional independence, intellectual performance and academic achievement of children treated for medulloblastoma at the Veterans General Hospital-Taipei. Adverse factors that it was thought would result in significant intellectual impairment were also studied. Nineteen patients with medulloblastoma located over the posterior fossa were enrolled in this study. Their mean age at tumor removal was 6.16 +/- 3.30 (range 2-14) years. Mean full intelligent quotient (FIQ) was 86.00 +/- 22.66, performance intelligent quotient (PIQ) was 85.29 +/- 21.23, and verbal intelligent quotient (VIQ) was 90.50 +/- 23.50. In 11 cases academic achievement at school was poor. Sixteen patients received radiation therapy after tumor removal. Significant negative correlations were noted between IQ and whole-brain irradiation dose (r = -0.72) and between IQ and years after radiation therapy (r = -0.63). The results indicate a need for ongoing attention and intervention to prevent, remedy or minimize deficits produced by the tumor itself and by the cancer treatment.

Effects of IFN-gamma, TNF-alpha and EGF on the expression of HLA class I antigen and the proliferation of human hepatocellular carcinoma HepG2 cells.

In this study, the effects of IFN gamma, TNF alpha and EGF on the expression of HLA class I antigen and the proliferation of human hepatocellular carcinoma-HepG2 cells were investigated. In response to IFN gamma or TNF alpha stimulation, the expression of HLA class I mRNA in HepG2 cells was increased by 2-4 fold. Cell surface HLA class I antigen was also increased, but in comparison, the increase was not as high as HLA class I mRNA expression. This is probably due to the limitation of protein translational and post-translational processing. The enhancing effect of EGF on cell surface HLA class I antigen could be noted but was not very significant. IFN gamma and TNF alpha could also inhibit the proliferation of HepG2 cells. Interestingly, the effect of EGF on the proliferation of HepG2 cells depended on its concentration. At low concentrations, EGF increased cell proliferation in terms of thymidine incorporation. However, if the concentration of EGF was relatively high, it could also exert an inhibitory effect on thymidine incorporation into HepG2 cells. The remarkable morphological alteration was observed when HepG2 cells were exposed to EGF at concentrations higher than 5 ng/ml. This morphological alteration might be associated with the inhibitory effect of EGF at high concentrations on the proliferation of HepG2 cells.

Modulation of EGF receptor by tumor necrosis factor-alpha in human hepatocellular carcinoma HepG2 cells.

TNF alpha is known to exert multi-regulatory effects on normal and malignant cell functions by binding to the corresponding cell surface receptor. However, the existence of cross interaction between TNF alpha and EGF receptor has been proposed. In this study, we investigated the modulatory effect of TNF alpha on EGF receptor of a human hepatocellular carcinoma cell line-HepG2. The results suggested that TNF alpha was able to modulate the EGF receptor of HepG2 cells. The modulatory effect of TNF alpha on the EGF receptor of HepG2 cells exhibited its unique characteristics in comparison with the previous reports on other tumor cells. TNF alpha could also enhance the tyrosine phosphorylation of the EGF receptor of HepG2 cells. However, the effect appeared only if EGF was present, and was not mediated by TNF alpha alone. Therefore, the effect of TNF alpha on EGF receptor tyrosine phosphorylation in HepG2 cells was due to enhancing the receptor's response to EGF. TNF alpha was also able to reduce the affinity of the high-affinity receptor for EGF. However, there was no significant alteration in terms of the expression of EGF receptor, EGF internalization, or EGF degradation when HepG2 cells were treated with TNF alpha. Since TNF alpha is an inhibitory agent for HepG2 cell growth, this cross interaction between TNF alpha and EGF receptor may play a role in the inhibition of cell growth.

Genistein, a tyrosine kinase inhibitor, reduces EGF-induced EGF receptor internalization and degradation in human hepatoma HepG2 cells.

In this work, using the ECL Western blotting assay system, it was found that genistein, a specific tyrosine kinase inhibitor, was able to inhibit EGF-induced EGF receptor degradation and tyrosine phosphorylation in human hepatoma HepG2 cells. This inhibition was increased with increasing genistein concentration. With treatment of HepG2 cells with genistein at 37 degrees C for 30 min, the amount of internalized EGF, which was measured by the detection of the sorting of 125I-EGF in the cells, was remarkably decreased. Under the same conditions, in cells untreated with genistein, the degradation of EGF was significantly increased. After preincubation of HepG2 cells with and without genistein for 120 min at 37 degrees C, the ratio between degraded and released EGF was 16 and 24, respectively. These results suggest that EGF-induced internalization and degradation of EGF-EGF receptor complexes in HepG2 cells depend on EGF receptor tyrosine kinase activity.