Connexin-43 can delay early recurrence and metastasis in patients with hepatitis B-related hepatocellular carcinoma and low serum alpha-fetoprotein after radical hepatectomy
We studied the relationships among Cx43, CD105, and VEGF in specimens of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) with different serum AFP levels with respect to recurrence and metastasis.
Low expression of N-myc downstream-regulated gene 2 in oesophageal squamous c...Enrique Moreno Gonzalez
It is currently unclear whether a correlation exists between N-myc downstream-regulated gene 2 (NDRG2) expression and oesophageal squamous cell carcinoma (ESCC). The aim of this study was to examine the underlying clinical significance of NDRG2 expression in ESCC patients and to investigate the effects of NDRG2 up-regulation on ESCC cell growth in vitro and in vivo.
Abnormal expression of Pygopus 2 correlates with a malignant phenotype in hum...Enrique Moreno Gonzalez
Pygopus 2 (Pygo2) is a Pygo family member and an important component of the Wnt signaling transcriptional complex. Despite this data, no clinical studies investigating Pygo2 expression in lung cancer have yet been reported.
Low expression of N-myc downstream-regulated gene 2 in oesophageal squamous c...Enrique Moreno Gonzalez
It is currently unclear whether a correlation exists between N-myc downstream-regulated gene 2 (NDRG2) expression and oesophageal squamous cell carcinoma (ESCC). The aim of this study was to examine the underlying clinical significance of NDRG2 expression in ESCC patients and to investigate the effects of NDRG2 up-regulation on ESCC cell growth in vitro and in vivo.
Abnormal expression of Pygopus 2 correlates with a malignant phenotype in hum...Enrique Moreno Gonzalez
Pygopus 2 (Pygo2) is a Pygo family member and an important component of the Wnt signaling transcriptional complex. Despite this data, no clinical studies investigating Pygo2 expression in lung cancer have yet been reported.
BACKGROUND: Sequential Epstein-Barr virus (EBV)–positive B cell lymphoma to the initial diagnosis of angioimmunoblastic T cell lymphoma (AITL) is very rare, the exact mechanism and standard therapy of which is still being explored. CASE: A 50-year-old man was admitted to our hospital in January 2014 with a three-week history of enlargement of multiple lymph nodes. His initial pathological evaluation indicated AILT. The reactivation of EBV was observed during the immunosuppression therapy for AITL, accompanied by onset of subcutaneous nodules proven to be EBV-positive diffuse large B cell lymphoma (DLBCL) based on the pathological findings of rebiopsy. The patient was successfully treated with chidamide, a histone deacetylase (HDAC) inhibitor, and rituximab.
Conclusion: The sufficient surveillance for serum EBV and repeat biopsy is necessary for patients with AITL, and this treatment modality may become an active option.
Keywords: angioimmunoblastic T cell lymphoma, Epstein-Barr virus, HDAC inhibitor, non-Hodgkin lymphoma, peripheral T cell lymphoma
Recently, a phase II clinical trial in hepatocellular carcinoma (HCC) has suggested that the combination of sorafenib and 5-fluorouracil (5-FU) is feasible and side effects are manageable. However, preclinical experimental data explaining the interaction mechanism(s) are lacking. Our objective is to investigate the anticancer efficacy and mechanism of combined sorafenib and 5-FU therapy in vitro in HCC cell lines MHCC97H and SMMC-7721.
Clinical and experimental studies regarding the expression and diagnostic val...Enrique Moreno Gonzalez
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a multifunctional Ig-like cell adhesion molecule that has a wide range of biological functions. According to previous reports, serum CEACAM1 is dysregulated in different malignant tumours and associated with tumour progression. However, the serum CEACAM1 expression in nonsmall-cell lung carcinomas (NSCLC) is unclear. The different expression ratio of CEACAM1-S and CEACAM1-L isoform has seldom been investigated in NSCLC. This research is intended to study the serum CEACAM1 and the ratio of CEACAM1-S/L isoforms in NSCLC.
IMMUNOHISTOCHEMICAL ALTERATIONS IN HEPATOCELLULAR CARCINOMA PATIENTS TREATED ...Jing Zang
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Doxorubicin (Dox) is an anthracycline antibiotic used as a single chemotherapeutic agent for HCC. The present work was conducted to study the immunohistochemical alterations in HCC patients treated with Dox. Thirty cases (24 males and 6 female) with a confirmed diagnosis of hepatocellular carcinoma (HCC) were used. They were divided into 3 groups, group 1. Ten specimens of HCC were taken before Dox treatments, group 2.Ten specimens HCC patients were taken one week after Dox treatment and group 3.Ten specimens of HCC patients were taken two weeks after Dox treatment. Hepatic biopsies were obtained from the three groups and prepared for histological, immunohistochemical (p53, Bcl-2 and CD34) and molecular studies. Histological examination of the specimen of HCC patients, before and after Dox treatment, showed trabecular appeareance, cytoplasmic vacuolation of the hepatocytes, fatty degeneration and necrosis. Cirrhosis appeared in 40% of the patients before treatment and 40% and 30% after one week and 2 weeks of treatment, respectively. Imunohistochemical results revealed an increase in expression of p53, CD34 and Bcl-2 in HCC patients. Overexpression of p53, decrease of Bcl-2 and mild degree of expression of CD34 was recorded in patients treated with Dox. Significant increase in DNA fragmentation was recorded in HCC patients treated by Dox in comparison with untreated HCC.
Overexpression of YAP 1 contributes to progressive features and poor prognosi...Enrique Moreno Gonzalez
Yes-associated protein 1 (YAP 1), the nuclear effector of the Hippo pathway, is a key regulator of organ size and a candidate human oncogene in multiple tumors. However, the expression dynamics of YAP 1 in urothelial carcinoma of the bladder (UCB) and its clinical/prognostic significance are unclear.
Objective: Tongue squamous cell carcinoma (TSCC) is a prominent type of oral cancer. Despite the numerous research studies on SCC and microRNAs (miRs), the relation between TSCC and miR-135b-5p is poorly discussed. This experiment aims to find out the possible effect of miR-135b-5p on TSCC with the network of its downstream genes.
Study Design: TSCC tissues and adjacent normal tissues were harvested. Then, expression of miR-135b-5p and AT-rich interactive domain‑containing protein 1A gene (ARID1A) and the phosphatidyl inositol 3-kinase/protein kinase B (PI3K/AKT) pathway was analyzed. After the transfection of miR-135b-5p inhibitor and its negative control into TSCC cells, functional assays were employed to measure cell proliferation, apoptosis, and cycle. Next, the target relation between miR-135b-5p and ARID1A was confirmed. In addition, the fact that miR-135b-5p promoted TSCC development via mediating ARID1A was demonstrated by functional rescue experiment.
Results: miR-135b-5p was upregulated in TSCC tissues and cells, while ARID1A was suppressed (p< 0.05). Silenced miR-135b-5p discouraged TSCC cell proliferation, improved apoptosis, induced cell cycle arrest, and increased ARID1A expression while inactivating the PI3K/AKT axis (p<0.05). Furthermore, knockdown of ARID1A reversed the impacts on TSCC cell proliferation and apoptosis exerted by silencing miR-135b-5p.
Conclusion: This research supported that silenced miR-135b-5p impeded TSCC proliferation and apoptosis by promoting ARID1A and inactivating the PI3K/AKT axis, which may provide some indications for TSCC alleviation.
Keywords: apoptosis; ARID1A; ARID1A protein, human; carcinoma, squamous cell; cell line, tumor; cell proliferation; drug resistance, neoplasm; microRNA-135b-5p; microRNAs; PI3K/AKT pathway; neoplasm metastasis; neoplastic stem cells; proliferation; protein binding; tongue; tongue squamous cell carcinoma
Differences in microRNA expression during tumor development in the transition...Enrique Moreno Gonzalez
The prostate is divided into three glandular zones, the peripheral zone (PZ), the transition zone (TZ), and the central zone. Most prostate tumors arise in the peripheral zone (70-75%) and in the transition zone (20-25%) while only 10% arise in the central zone. The aim of this study was to investigate if differences in miRNA expression could be a possible explanation for the difference in propensity of tumors in the zones of the prostate.
Impaired mitochondrial beta-oxidation in patients with chronic hepatitis C: r...Enrique Moreno Gonzalez
Hepatic steatosis is often seen in patients with chronic hepatitis C (CH-C). It is still unclear whether these patients have an impaired mitochondrial β-oxidation. In this study we assessed mitochondrial β-oxidation in CH-C patients by investigating ketogenesis during fasting.
Alterations of the genes involved in the PI3K and estrogen-receptor pathways ...Enrique Moreno Gonzalez
Chemotherapy with trastuzumab is widely used for patients with human epidermal growth
factor receptor 2-positive (HER2+) breast cancer, but a significant number of patients with
the tumor fail to respond, or relapse. The mechanisms of recurrence and biomarkers that indicate the response to the chemotherapy and outcome are not fully investigated.
Polymorphism of A133S and promoter hypermethylation in Ras association domain...Enrique Moreno Gonzalez
The role of tumor suppressor gene RASSF1A in the esophageal and gastric cardia carcinogenesis is still inconclusive. In this study, the polymorphism, promoter methylation and gene expression of RASSF1A were characterized in esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA).
Potentiality of a triple microRNA classifier: miR- 193a-3p, miR-23a and miR-3...Enrique Moreno Gonzalez
MicroRNAs (miRNAs) are short, non-coding RNA molecules that act as regulators of gene expression. Circulating blood miRNAs offer great potential as cancer biomarkers. The objective of this study was to correlate the differential expression of miRNAs in tissue and blood in the identification of biomarkers for early detection of colorectal cancer (CRC).
BACKGROUND: Sequential Epstein-Barr virus (EBV)–positive B cell lymphoma to the initial diagnosis of angioimmunoblastic T cell lymphoma (AITL) is very rare, the exact mechanism and standard therapy of which is still being explored. CASE: A 50-year-old man was admitted to our hospital in January 2014 with a three-week history of enlargement of multiple lymph nodes. His initial pathological evaluation indicated AILT. The reactivation of EBV was observed during the immunosuppression therapy for AITL, accompanied by onset of subcutaneous nodules proven to be EBV-positive diffuse large B cell lymphoma (DLBCL) based on the pathological findings of rebiopsy. The patient was successfully treated with chidamide, a histone deacetylase (HDAC) inhibitor, and rituximab.
Conclusion: The sufficient surveillance for serum EBV and repeat biopsy is necessary for patients with AITL, and this treatment modality may become an active option.
Keywords: angioimmunoblastic T cell lymphoma, Epstein-Barr virus, HDAC inhibitor, non-Hodgkin lymphoma, peripheral T cell lymphoma
Recently, a phase II clinical trial in hepatocellular carcinoma (HCC) has suggested that the combination of sorafenib and 5-fluorouracil (5-FU) is feasible and side effects are manageable. However, preclinical experimental data explaining the interaction mechanism(s) are lacking. Our objective is to investigate the anticancer efficacy and mechanism of combined sorafenib and 5-FU therapy in vitro in HCC cell lines MHCC97H and SMMC-7721.
Clinical and experimental studies regarding the expression and diagnostic val...Enrique Moreno Gonzalez
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a multifunctional Ig-like cell adhesion molecule that has a wide range of biological functions. According to previous reports, serum CEACAM1 is dysregulated in different malignant tumours and associated with tumour progression. However, the serum CEACAM1 expression in nonsmall-cell lung carcinomas (NSCLC) is unclear. The different expression ratio of CEACAM1-S and CEACAM1-L isoform has seldom been investigated in NSCLC. This research is intended to study the serum CEACAM1 and the ratio of CEACAM1-S/L isoforms in NSCLC.
IMMUNOHISTOCHEMICAL ALTERATIONS IN HEPATOCELLULAR CARCINOMA PATIENTS TREATED ...Jing Zang
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Doxorubicin (Dox) is an anthracycline antibiotic used as a single chemotherapeutic agent for HCC. The present work was conducted to study the immunohistochemical alterations in HCC patients treated with Dox. Thirty cases (24 males and 6 female) with a confirmed diagnosis of hepatocellular carcinoma (HCC) were used. They were divided into 3 groups, group 1. Ten specimens of HCC were taken before Dox treatments, group 2.Ten specimens HCC patients were taken one week after Dox treatment and group 3.Ten specimens of HCC patients were taken two weeks after Dox treatment. Hepatic biopsies were obtained from the three groups and prepared for histological, immunohistochemical (p53, Bcl-2 and CD34) and molecular studies. Histological examination of the specimen of HCC patients, before and after Dox treatment, showed trabecular appeareance, cytoplasmic vacuolation of the hepatocytes, fatty degeneration and necrosis. Cirrhosis appeared in 40% of the patients before treatment and 40% and 30% after one week and 2 weeks of treatment, respectively. Imunohistochemical results revealed an increase in expression of p53, CD34 and Bcl-2 in HCC patients. Overexpression of p53, decrease of Bcl-2 and mild degree of expression of CD34 was recorded in patients treated with Dox. Significant increase in DNA fragmentation was recorded in HCC patients treated by Dox in comparison with untreated HCC.
Overexpression of YAP 1 contributes to progressive features and poor prognosi...Enrique Moreno Gonzalez
Yes-associated protein 1 (YAP 1), the nuclear effector of the Hippo pathway, is a key regulator of organ size and a candidate human oncogene in multiple tumors. However, the expression dynamics of YAP 1 in urothelial carcinoma of the bladder (UCB) and its clinical/prognostic significance are unclear.
Objective: Tongue squamous cell carcinoma (TSCC) is a prominent type of oral cancer. Despite the numerous research studies on SCC and microRNAs (miRs), the relation between TSCC and miR-135b-5p is poorly discussed. This experiment aims to find out the possible effect of miR-135b-5p on TSCC with the network of its downstream genes.
Study Design: TSCC tissues and adjacent normal tissues were harvested. Then, expression of miR-135b-5p and AT-rich interactive domain‑containing protein 1A gene (ARID1A) and the phosphatidyl inositol 3-kinase/protein kinase B (PI3K/AKT) pathway was analyzed. After the transfection of miR-135b-5p inhibitor and its negative control into TSCC cells, functional assays were employed to measure cell proliferation, apoptosis, and cycle. Next, the target relation between miR-135b-5p and ARID1A was confirmed. In addition, the fact that miR-135b-5p promoted TSCC development via mediating ARID1A was demonstrated by functional rescue experiment.
Results: miR-135b-5p was upregulated in TSCC tissues and cells, while ARID1A was suppressed (p< 0.05). Silenced miR-135b-5p discouraged TSCC cell proliferation, improved apoptosis, induced cell cycle arrest, and increased ARID1A expression while inactivating the PI3K/AKT axis (p<0.05). Furthermore, knockdown of ARID1A reversed the impacts on TSCC cell proliferation and apoptosis exerted by silencing miR-135b-5p.
Conclusion: This research supported that silenced miR-135b-5p impeded TSCC proliferation and apoptosis by promoting ARID1A and inactivating the PI3K/AKT axis, which may provide some indications for TSCC alleviation.
Keywords: apoptosis; ARID1A; ARID1A protein, human; carcinoma, squamous cell; cell line, tumor; cell proliferation; drug resistance, neoplasm; microRNA-135b-5p; microRNAs; PI3K/AKT pathway; neoplasm metastasis; neoplastic stem cells; proliferation; protein binding; tongue; tongue squamous cell carcinoma
Differences in microRNA expression during tumor development in the transition...Enrique Moreno Gonzalez
The prostate is divided into three glandular zones, the peripheral zone (PZ), the transition zone (TZ), and the central zone. Most prostate tumors arise in the peripheral zone (70-75%) and in the transition zone (20-25%) while only 10% arise in the central zone. The aim of this study was to investigate if differences in miRNA expression could be a possible explanation for the difference in propensity of tumors in the zones of the prostate.
Impaired mitochondrial beta-oxidation in patients with chronic hepatitis C: r...Enrique Moreno Gonzalez
Hepatic steatosis is often seen in patients with chronic hepatitis C (CH-C). It is still unclear whether these patients have an impaired mitochondrial β-oxidation. In this study we assessed mitochondrial β-oxidation in CH-C patients by investigating ketogenesis during fasting.
Alterations of the genes involved in the PI3K and estrogen-receptor pathways ...Enrique Moreno Gonzalez
Chemotherapy with trastuzumab is widely used for patients with human epidermal growth
factor receptor 2-positive (HER2+) breast cancer, but a significant number of patients with
the tumor fail to respond, or relapse. The mechanisms of recurrence and biomarkers that indicate the response to the chemotherapy and outcome are not fully investigated.
Polymorphism of A133S and promoter hypermethylation in Ras association domain...Enrique Moreno Gonzalez
The role of tumor suppressor gene RASSF1A in the esophageal and gastric cardia carcinogenesis is still inconclusive. In this study, the polymorphism, promoter methylation and gene expression of RASSF1A were characterized in esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA).
Potentiality of a triple microRNA classifier: miR- 193a-3p, miR-23a and miR-3...Enrique Moreno Gonzalez
MicroRNAs (miRNAs) are short, non-coding RNA molecules that act as regulators of gene expression. Circulating blood miRNAs offer great potential as cancer biomarkers. The objective of this study was to correlate the differential expression of miRNAs in tissue and blood in the identification of biomarkers for early detection of colorectal cancer (CRC).
The effect of different dosing regimens of motesanib on the gallbladder: a ra...Enrique Moreno Gonzalez
Gallbladder toxicity, including cholecystitis, has been reported with motesanib, an orally administered small-molecule antagonist of VEGFRs 1, 2 and 3; PDGFR; and Kit. We assessed effects of motesanib on gallbladder size and function.
Rectal forceps biopsy procedure in cystic fibrosis: technical aspects and pat...Enrique Moreno Gonzalez
Measurements of CFTR function in rectal biopsies ex vivo have been used for diagnosis and
prognosis of Cystic Fibrosis (CF) disease. Here, we aimed to evaluate this procedure
regarding: i) viability of the rectal specimens obtained by biopsy forceps for ex vivo
bioelectrical and biochemical laboratory analyses; and ii) overall assessment (comfort,
invasiveness, pain, sedation requirement, etc.) of the rectal forceps biopsy procedure from the
patients perspective to assess its feasibility as an outcome measure in clinical trials.
Clinical outcome, proteome kinetics and angiogenic factors in serum after the...Enrique Moreno Gonzalez
Thermoablation is used to treat patients with unresectable colorectal liver metastases (CRLM). We analyze clinical outcome, proteome kinetics and angiogenic markers in patients treated by cryosurgical ablation (CSA) or radiofrequency ablation (RFA).
Preventive effect of irsogladine or omeprazole on non-steroidal anti-inflamma...Enrique Moreno Gonzalez
Proton-pump inhibitors such as omeprazole are a standard treatment to prevent non-steroidal
anti-inflammatory drug-induced upper gastrointestinal mucosal injuries. However, it is
unclear which drugs may protect against all NSAID-induced digestive-tract injuries. Here, we
compare the efficacy of the gastromucoprotective drug irsogladine with omeprazole in
preventing NSAID-induced esophagitis, peptic ulcers, and small-intestinal mucosal injury in
healthy subjects.
Acute myeloid leukemia (AML) is a hematopoietic malignancy with a dismal outcome in the majority of cases. A detailed understanding of the genetic alterations and gene expression changes that contribute to its pathogenesis is important to improve prognostication, disease monitoring, and therapy. In this context, leukemia-associated misexpression of microRNAs (miRNAs) has been studied, but no coherent picture has emerged yet, thus warranting further investigations.
Incidence of pneumonia and risk factors among patients with head and neck can...Enrique Moreno Gonzalez
This study investigated the incidence and patient- and treatment-related risk factors related to pneumonia acquired during radiotherapy (PNRT) in head and neck cancer (HNC) patients.
Incidence of pneumonia and risk factors among patients with head and neck can...
Similar to Connexin-43 can delay early recurrence and metastasis in patients with hepatitis B-related hepatocellular carcinoma and low serum alpha-fetoprotein after radical hepatectomy
10-Year survival of GCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) GC characteristics; 9) anthropometric data; 10) surgery type. Optimal diagnosis and treatment strategies for GC are: 1) screening and early detection of GC; 2) availability of experienced abdominal surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunotherapy for GCP with unfavorable prognosis.
Detailed Information regarding MSKCC,IMDC score with evidence .
SSIGN Score, Fuhrman's grading described .
Prognostic significance of risk score explained
Circulating Tumor Cells and Cell-Free Nucleic Acids as Predictor Factors for ...daranisaha
Pancreatic cancer remains as one of the most aggressive and deadliest of cancers largely due to formidable challenges in diagnosis and therapy. Consensus standard treatment for patients with nonmetastatic Pancreatic Cancer (PC) incorporates possible neoadjuvant chemotherapy with timely surgical resection and adjuvant chemotherapy. However, despite all the sophistication of modern radiological and endoscopic techniques, the decision regarding operability is often only made intra-operatively, therefore subjecting a patient to unnecessary surgical intervention, and postponing the possibility of starting early chemotherapy.
Circulating Tumor Cells and Cell-Free Nucleic Acids as Predictor Factors for ...AnonIshanvi
Pancreatic cancer remains as one of the most aggressive and deadliest of cancers largely due to formidable challenges in diagnosis and therapy. Consensus standard treatment for patients with nonmetastatic Pancreatic Cancer (PC) incorporates possible neoadjuvant chemotherapy with timely surgical resection and adjuvant chemotherapy. However, despite all the sophistication of modern radiological and endoscopic techniques, the decision regarding operability is often only made intra-operatively, therefore subjecting a patient to unnecessary surgical intervention, and postponing the possibility of starting early chemotherapy.
Circulating Tumor Cells and Cell-Free Nucleic Acids as Predictor Factors for ...JohnJulie1
Pancreatic cancer remains as one of the most aggressive and deadliest of cancers largely due to formidable challenges in diagnosis and therapy. Consensus standard treatment for patients with nonmetastatic Pancreatic Cancer (PC) incorporates possible neoadjuvant chemotherapy with timely surgical resection and adjuvant chemotherapy. However, despite all the sophistication of modern radiological and endoscopic techniques, the decision regarding operability is often only made intra-operatively, therefore subjecting a patient to unnecessary surgical intervention, and postponing the possibility of starting early chemotherapy.
Circulating Tumor Cells and Cell-Free Nucleic Acids as Predictor Factors for ...semualkaira
Pancreatic cancer remains as one of the most
aggressive and deadliest of cancers largely due to formidable challenges in diagnosis and therapy. Consensus standard treatment for
patients with nonmetastatic Pancreatic Cancer (PC) incorporates
possible neoadjuvant chemotherapy with timely surgical resection
and adjuvant chemotherapy. However, despite all the sophistication of modern radiological and endoscopic techniques, the decision regarding operability is often only made intra-operatively,
therefore subjecting a patient to unnecessary surgical intervention,
and postponing the possibility of starting early chemotherapy.
Circulating Tumor Cells and Cell-Free Nucleic Acids as Predictor Factors for ...EditorSara
Pancreatic cancer remains as one of the most aggressive and deadliest of cancers largely due to formidable challenges in diagnosis and therapy. Consensus standard treatment for patients with nonmetastatic Pancreatic Cancer (PC) incorporates possible neoadjuvant chemotherapy with timely surgical resection and adjuvant chemotherapy. However, despite all the sophistication of modern radiological and endoscopic techniques, the decision regarding operability is often only made intra-operatively, therefore subjecting a patient to unnecessary surgical intervention, and postponing the possibility of starting early chemotherapy.
Circulating Tumor Cells and Cell-Free Nucleic Acids as Predictor Factors for ...EditorSara
Pancreatic cancer remains as one of the most aggressive and deadliest of cancers largely due to formidable challenges in diagnosis and therapy. Consensus standard treatment for patients with nonmetastatic Pancreatic Cancer (PC) incorporates possible neoadjuvant chemotherapy with timely surgical resection and adjuvant chemotherapy. However, despite all the sophistication of modern radiological and endoscopic techniques, the decision regarding operability is often only made intra-operatively, therefore subjecting a patient to unnecessary surgical intervention, and postponing the possibility of starting early chemotherapy.
Circulating Tumor Cells and Cell-Free Nucleic Acids as Predictor Factors for ...semualkaira
Pancreatic cancer remains as one of the most
aggressive and deadliest of cancers largely due to formidable challenges in diagnosis and therapy. Consensus standard treatment for
patients with nonmetastatic Pancreatic Cancer (PC) incorporates
possible neoadjuvant chemotherapy with timely surgical resection
and adjuvant chemotherapy
Circulating Tumor Cells and Cell-Free Nucleic Acids as Predictor Factors for ...semualkaira
Pancreatic cancer remains as one of the most aggressive and deadliest of cancers largely due to formidable challenges in diagnosis and therapy. Consensus standard treatment for patients with nonmetastatic Pancreatic Cancer (PC) incorporates possible neoadjuvant chemotherapy with timely surgical resection and adjuvant chemotherapy. However, despite all the sophistication of modern radiological and endoscopic techniques, the decision regarding operability is often only made intra-operatively, therefore subjecting a patient to unnecessary surgical intervention, and postponing the possibility of starting early chemotherapy.
Circulating Tumor Cells and Cell-Free Nucleic Acids as Predictor Factors for ...NainaAnon
Pancreatic cancer remains as one of the most aggressive and deadliest of cancers largely due to formidable challenges in diagnosis and therapy. Consensus standard treatment for patients with nonmetastatic Pancreatic Cancer (PC) incorporates possible neoadjuvant chemotherapy with timely surgical resection and adjuvant chemotherapy. However, despite all the sophistication of modern radiological and endoscopic techniques, the decision regarding operability is often only made intra-operatively, therefore subjecting a patient to unnecessary surgical intervention, and postponing the possibility of starting early chemotherapy.
Circulating Tumor Cells and Cell-Free Nucleic Acids as Predictor Factors for ...semualkaira
Pancreatic cancer remains as one of the most
aggressive and deadliest of cancers largely due to formidable challenges in diagnosis and therapy. Consensus standard treatment for
patients with nonmetastatic Pancreatic Cancer (PC) incorporates
possible neoadjuvant chemotherapy with timely surgical resection
and adjuvant chemotherapy
Molecular characterization of a patient’s tumor to guide treatment decisions is increasingly being
applied in clinical care and can have a significant impact on disease outcome. These molecular analyses,
including mutation characterization, are typically performed on tissue acquired through a biopsy at diagnosis.
However, tumors are highly heterogeneous and sampling in its entirety is challenging. Furthermore, tumors
evolve over time and can alter their molecular genotype, making clinical decisions based on historical biopsy
data suboptimal. Personalized medicine for cancer patients aims to tailor the best treatment options for the
individual at diagnosis and during treatment. To fully enable personalized medicine it is desirable to have an
easily accessible, minimally invasive way to determine and follow the molecular makeup of a patient’s tumor
longitudinally. One such approach is through a liquid biopsy, where the genetic makeup of the tumor can be
assessed through a bio fluid sample. Liquid biopsies have the potential to help clinicians screen for disease,
stratify patients to the best treatment and monitor treatment response and resistance mechanisms in the tumor. A liquid biopsy can be used for molecular characterization of the tumor and its non-invasive nature
allows repeat sampling to monitor genetic changes over time without the need for a tissue biopsy. This review will summarize three approaches in the liquid biopsy field: circulating tumor cells (CTCs), cell free DNA (cfDNA) and exosomes. We also outline some of the analytical challenges encountered using liquid biopsy techniques to detect rare mutations in a background of wild-type sequences.
Increased Expression of GNL3L is Associated with Aggressive Phenotypes in Col...JohnJulie1
Guanine nucleotide binding protein-like 3-like (GNL3L) plays critical roles in development and progression of several types of human cancers. However, the function and clinical significance of GNL3L in colorectal cancer (CRC) remain unclear. In this study, the effect of GNL3L in CRC and its underlying mechanism were investigated.
Similar to Connexin-43 can delay early recurrence and metastasis in patients with hepatitis B-related hepatocellular carcinoma and low serum alpha-fetoprotein after radical hepatectomy (20)
Gene expression analysis of a Helicobacter pyloriinfected and high-salt diet-...Enrique Moreno Gonzalez
Helicobacter pylori (H. pylori) infection and excessive salt intake are known as important risk factors for stomach cancer in humans. However, interactions of these two factors with gene expression profiles during gastric carcinogenesis remain unclear. In the present study, we investigated the global gene expression associated with stomach carcinogenesis and prognosis of human gastric cancer using a mouse model.
Multicentric and multifocal versus unifocal breast cancer: differences in the...Enrique Moreno Gonzalez
The aim of this study was to evaluate the expression of the cell adhesion-related glycoproteins MUC-1, β-catenin and E-cadherin in multicentric/multifocal breast cancer in comparison to unifocal disease in order to identify potential differences in the biology of these tumor types.
The life in sight application study (LISA): design of a randomized controlled...Enrique Moreno Gonzalez
It is widely recognized that spiritual care plays an important role in physical and psychosocial well-being of cancer patients, but there is little evidence based research on the effects of spiritual care. We will conduct a randomized controlled trial on spiritual care using a brief structured interview scheme supported by an e-application. The aim is to examine whether an assisted reflection on life events and ultimate life goals can improve quality of life of cancer patients.
Assessment of preoperative exercise capacity in hepatocellular carcinoma pati...Enrique Moreno Gonzalez
Cardiopulmonary exercise testing measures oxygen uptake at increasing levels of work and predicts cardiopulmonary performance under conditions of stress, such as after abdominal surgery. Dynamic assessment of preoperative exercise capacity may be a useful predictor of postoperative prognosis. This study examined the relationship between preoperative exercise capacity and event-free survival in hepatocellular carcinoma (HCC) patients with chronic liver injury who underwent hepatectomy.
CXCR7 is induced by hypoxia and mediates glioma cell migration towards SDF-1a...Enrique Moreno Gonzalez
Glioblastomas, the most common and malignant brain tumors of the central nervous system, exhibit high invasive capacity, which hinders effective therapy. Therefore, intense efforts aimed at improved therapeutics are ongoing to delineate the molecular mechanisms governing glioma cell migration and invasion.
Differentiation of irradiation and cetuximab induced skin reactions in patien...Enrique Moreno Gonzalez
In order to improve the clinical outcome of patients with locally advanced squamous cell carcinoma of the head and neck (LASCCHN) not being capable to receive platinum-based chemoradiation, radiotherapy can be intensified by addition of cetuximab, a monoclonal antibody that blocks the epidermal growth factor receptor (EGFR). The radioimmunotherapy with cetuximab is a feasible treatment option showing a favourable toxicity profile. The most frequent side effect of radiotherapy is radiation dermatitis, the most common side effect of treatment with cetuximab is acneiform rash. Incidence and severity of these frequent, often overlapping and sometimes limiting skin reactions, however, are not well explored. A clinical and molecular differentiation between radiogenic skin reactions and skin reactions caused by cetuximab which may correlate with outcome, have never been described before.
Cholestasis induces reversible accumulation of periplakin in mouse liverEnrique Moreno Gonzalez
Periplakin (PPL) is a rod-shaped cytolinker protein thought to connect cellular adhesion junctional complexes to cytoskeletal filaments. PPL serves as a structural component of the cornified envelope in the skin and interacts with various types of proteins in cultured cells; its level decreases dramatically during tumorigenic progression in human epithelial tissues. Despite these intriguing observations, the physiological roles of PPL, especially in noncutaneous tissues, are still largely unknown. Because we observed a marked fluctuation of PPL expression in mouse liver in association with the bile acid receptor farnesoid X receptor (FXR) and cholestasis, we sought to characterize the role of PPL in the liver and determine its contributions to the etiology and pathogenesis of cholestasis.
Functional p53 is required for rapid restoration of daunorubicin-induced lesi...Enrique Moreno Gonzalez
The tumour suppressor and transcription factor p53 is a major determinant of the therapeutic response to anthracyclines. In healthy tissue, p53 is also considered pivotal for side effects of anthracycline treatment such as lesions in haematopoietic tissues like the spleen. We used a Trp53null mouse to explore the significance of p53 in anthracycline (daunorubicin) induced lesions in the spleen.
Post-diagnosis hemoglobin change associates with overall survival of multiple...Enrique Moreno Gonzalez
Anemia refers to low hemoglobin (Hb) level and is a risk factor of cancer patient survival. The National Comprehensive Cancer Network recently suggested that post-diagnosis Hb change, regardless of baseline Hb level, indicates the potential presence of anemia. However, there is no epidemiological study evaluating whether Hb change has direct prognostic values for cancer patients at the population level.
Cost-effectiveness of MRI for breast cancer screening in BRCA1/2 mutation car...Enrique Moreno Gonzalez
Women with mutations in BRCA1 or BRCA2 are at high risk of developing breast cancer and, in British Columbia, Canada, are offered screening with both magnetic resonance imaging (MRI) and mammography to facilitate early detection. MRI is more sensitive than mammography but is more costly and produces more false positive results. The purpose of this study was to calculate the cost-effectiveness of MRI screening for breast cancer in BRCA1/2 mutation carriers in a Canadian setting.
Intraepithelial lymphocyte distribution differs between the bulb and the seco...Enrique Moreno Gonzalez
Evaluation of intraepithelial duodenal lymphocytosis (IDL) is important in celiac disease (CD). There is no established cut-off value for increased number of IELs in the bulb. We therefore investigated the relation between IEL counts in the bulb and duodenal specimens in non-celiac subjects.
Sticky siRNAs targeting survivin and cyclin B1 exert an antitumoral effect on...Enrique Moreno Gonzalez
Melanoma represents one of the most aggressive and therapeutically challenging malignancies as it often gives rise to metastases and develops resistance to classical chemotherapeutic agents. Although diverse therapies have been generated, no major improvement of the patient prognosis has been noticed. One promising alternative to the conventional therapeutic approaches currently available is the inactivation of proteins essential for survival and/or progression of melanomas by means of RNA interference. Survivin and cyclin B1, both involved in cell survival and proliferation and frequently deregulated in human cancers, are good candidate target genes for siRNA mediated therapeutics.
Association between variations in the fat mass and obesity-associated gene an...Enrique Moreno Gonzalez
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The cysteinyl leukotriene 2 receptor contributes to all-trans retinoic acid-i...Enrique Moreno Gonzalez
Cysteinyl leukotrienes (CysLTs) are potent pro-inflammatory mediators that are increased in samples from patients with inflammatory bowel diseases (IBDs). Individuals with IBDs have enhanced susceptibility to colon carcinogenesis. In colorectal cancer, the balance between the pro-mitogenic cysteinyl leukotriene 1 receptor (CysLT1R) and the differentiation-promoting cysteinyl leukotriene 2 receptor (CysLT2R) is lost. Further, our previous data indicate that patients with high CysLT1R and low CysLT2R expression have a poor prognosis. In this study, we examined whether the balance between CysLT1R and CysLT2R could be restored by treatment with the cancer chemopreventive agent all-trans retinoic acid (ATRA).
Clinical features and outcome of cryptogenic hepatocellular carcinoma compare...Enrique Moreno Gonzalez
Cryptogenic hepatocellular carcinoma (HCC) is thought to arise due to non-alcoholic fatty liver disease (NAFLD). This study investigated the prevalence, clinical features, and outcomes of cryptogenic HCC and compared them with those of HCC related to hepatitis B virus infection (HBV-HCC), hepatitis C virus infection (HCV-HCC), and alcohol (ALCHCC) in Korea.
Fatty liver index correlates with non-alcoholic fatty liver disease, but not ...Enrique Moreno Gonzalez
Fatty liver index (FLI) was recently established to predict non-alcoholic fatty liver disease (NAFLD) in general population, which is known to be associated with coronary artery atherosclerotic disease (CAD).
This study aims to investigate whether FLI correlates with NAFLD and with newly diagnosed CAD in a special Chinese population who underwent coronary angiography.
Antibiotic exposure and the development of coeliac disease: a nationwide case...Enrique Moreno Gonzalez
The intestinal microbiota has been proposed to play a pathogenic role in coeliac disease (CD). Although antibiotics are common environmental factors with a profound impact on intestinal microbiota, data on antibiotic use as a risk factor for subsequent CD development are scarce.
Implication from thyroid function decreasing during chemotherapy in breast ca...Enrique Moreno Gonzalez
Thyroid hormones have been shown to regulate breast cancer cells growth, the absence or reduction of thyroid hormones in cells could provoke a proliferation arrest in G0-G1 or weak mitochondrial activity, which makes cells insensitive to therapies for cancers through transforming into low metabolism status. This biological phenomenon may help explain why treatment efficacy and prognosis vary among breast cancer patients having hypothyroid, hyperthyroid and normal function. Nevertheless, the abnormal thyroid function in breast cancer patients has been considered being mainly caused by thyroid diseases, few studied influence of chemotherapy on thyroid function and whether its alteration during chemotherapy can influence the respose to chemotherapy is still unclear. So, we aimed to find the alterations of thyroid function and non-thyroidal illness syndrome (NTIS) prevalence druing chemotherapy in breast cancer patients, and investigate the influence of thyroid hormones on chemotherapeutic efficacy.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
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Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
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comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Thyroid Gland- Gross Anatomy by Dr. Rabia Inam Gandapore.pptx
Connexin-43 can delay early recurrence and metastasis in patients with hepatitis B-related hepatocellular carcinoma and low serum alpha-fetoprotein after radical hepatectomy
2. Connexin-43 can delay early recurrence and
metastasis in patients with hepatitis B-related
hepatocellular carcinoma and low serum alpha-
fetoprotein after radical hepatectomy
Zu-Sen Wang1
Email: wangzusen@126.com
Li-Qun Wu1*
*
Corresponding author
Email: wulq5810@126.com
Xin Yi1
Email: sdqdyixin@126.com
Chao Geng1
Email: wfgch1986@163.com
Yu-Jun Li2
Email: yjli@126.com
Ru-Yong Yao3
Email: yry0303@163.com
1
Department of Hepatobiliary Surgery, Affiliated Hospital of Medical College
Qingdao University, Qingdao, Shandong Province 266003, China
2
Department of Pathology, Affiliated Hospital of Medical College Qingdao
University, Qingdao, Shandong Province 266003, China
3
Department of Central Laboratory, Affiliated Hospital of Medical College
Qingdao University, Qingdao, Shandong Province 266003, China
Abstract
Background
We studied the relationships among Cx43, CD105, and VEGF in specimens of hepatitis B
virus (HBV)-related hepatocellular carcinoma (HCC) with different serum AFP levels with
respect to recurrence and metastasis.
Methods
Expressions of Cx43, CD105, and VEGF in 234 HCC tissue specimens were examined using
tissue microarray and immunohistochemistry. Cx43 mRNA expression was examined in 38
frozen HCC specimens using RT-PCR. Correlations between these expressions and tumor
recurrence, metastasis, and prognosis were analyzed using Kaplan–Meier and Cox regression
analyses.
3. Results
Cx43 expression correlated with early tumor recurrence (P = 0.001), disease-free survival (P
= 0.026), and overall survival (P = 0.000) in patients with serum AFP < 400 ng/ml, but not in
those with serum AFP ≥ 400 µg/L. Cx43 expression is an independent predictor of later
recurrence and longer overall survival and is inversely correlated with expression of CD105
and VEGF (P = 0.018 and 0.023, respectively), histological differentiation (P = 0.002), vessel
tumor embolism (P = 0.029), and focal number (P = 0.017). Immunohistochemistry showed
that Cx43 expression in patients with low AFP was lower in patients with distant metastases
than in those with no metastasis or those with liver metastasis. Patients with early recurrence
expressed less Cx43 mRNA than did those with no recurrence (χ2
= 9.827, P = 0.002).
Conclusions
Cx43 expression can delay early HCC recurrence, metastasis, and poor prognosis after radical
hepatectomy in patients with HBV-related HCC and low AFP.
Keywords
Carcinoma, Hepatocellular, Hepatitis B, Alpha-fetoprotein, Cx43, VEGF, CD105, Early
recurrence, Metastasis, Prognosis
Background
Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third most
common cause of cancer death [1]. An estimated 748,300 new liver cancer cases and 695,900
cancer deaths occurred worldwide in 2008. [2] Although an increasing number of new
methods are now applied to treat these patients, surgery (including hepatectomy and liver
transplantation) is still the most important therapeutic approach for patients with HCC [3].
Transplantation is the preferred treatment option for small and resectable HCC [4], but its use
is limited by the lack of donor organs [5]. Although appropriate selection of patients with
HCC increases the clinical survival benefit after radical liver resection [6], the prognosis of
HCC remains poor because of the high rate of recurrence and metastases after radical
resection [7,8]. A primary research focus involves how to decrease the HCC recurrence and
metastasis rates worldwide.
Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections induce
approximately 75–80% of HCC in the world [9]. Chronic HBV infection accounts for about
60% of the total liver cancer in developing countries and about 23% of the cancer in
developed countries. This infection results in approximately one-third of all cases of liver
cirrhosis and more than three-quarters of all cases of HCC worldwide [10]. Serious
endemicity of HBV infection is present in China. In a literature review, Han et al. [11]
reported that a high serum viral load is the most reliable indicator of viral replication in
predicting development of HCC (serum viral load of ≥104
copies/mL for HCC occurrence
and 104
copies/mL for a poor prognosis). In addition, HBV genotype C is closely associated
with HCC in cirrhotic patients aged ≥50 years, whereas genotype B is associated with
development of HCC in noncirrhotic young patients (<50 years) and postoperative relapse of
HCC. Thus, we confined our investigation of HCC to patients with HBV-related HCC (HBV-
HCC) to reduce possible confounding variables, and we plan to study the relationship
4. between and mechanisms of early recurrence of HCC and HBV-related factors (e.g., serum
HBV viral load and HBV genotype and mutations).
Connexin-43 is a member of the connexin (Cx) protein family, which forms the basis of gap
junctions (GJs). GJs provide a medium through which GJ intercellular communication (GJIC)
is expressed; GJs are largely formed by Cx proteins. In liver tissue, GJIC mainly involves
three kinds of Cx—Cx26, Cx32, and Cx43—whose distribution depends on cell type and
location in the liver lobule [12]. HCC cells typically express high levels of Cx43, low levels
of Cx32, and no Cx26. Cx43, which is clearly expressed in HCC cells, is mainly located in
the cytoplasm; a small amount is located in areas connecting nonadjacent cells on the cell
membrane, which disrupts GJIC [13].
In this retrospective study, the protein expressions of Cx43, VEGF, and CD105 in HCC
tissue with different serum AFP levels were examined by tissue microarray and
immunohistochemical staining; expression of Cx43 mRNA was examined by RT-PCR to
explore the relationship between Cx43 and early recurrence, metastasis, and prognosis in
patients with HCC after radical resection.
Methods
Patients
Samples were taken from 249 patients with HBV-HCC who underwent radical resection from
January 2003 to December 2008 at the affiliated hospital of the Medical College of Qingdao
University. The study protocol was approved by the Ethics Committee of the Qingdao
University. All patients signed an informed consent form and met the medical ethics
requirements. Of these, 15 who underwent preoperative transcatheter arterial
chemoembolization were excluded; of the remaining 234 patients, 199 were male and 35
were female, with an average age of 54.2 years (range: 15–82 years). According to the TNM
classification (AJCC 7th edition, 2009), 137 patients were at Stage I, 30 were at Stage II, 63
were at Stage III, and 4 were at Stage IV. Control specimens were from adjacent
noncancerous tissue within 2 cm from the incisal margin (81 cases), and intraoperative
biopsies were from patients with portal hypertension (79 cases). Specimens from 38 patients
with HBV-HCC who underwent radical resection from January 2011 to June 2011 were
frozen by liquid nitrogen immediately and cryopreserved at –
80°C.
Tissue microarray and immunohistochemistry
A tissue arrayer (HT-1,beijing,china) was used to make 42 (6 × 7) 4-µm-thick lattice arrays,
which were first stained with hematoxylin/eosin to confirm the tissue type and then
immunohistochemically stained using PV-6000 methods (two steps), following the
manufacturer’s instructions. Briefly, PBS replaced the primary antibody as the negative
control; positive tissues were used as positive controls. Rabbit anti-human Cx43, VEGF, and
CD105 monoclonal antibodies as well as immunohistochemical detection reagents were
purchased from ZSGB-Bio Company (Beijing, China).
RT-PCR
RNAiso Plus and the PrimeScript RT-PCR Kit were produced by Takara Dalian (Dalian,
China). PCR Amplifier was produced by Eppendorf Company (Hamburg, Germany). The gel
electrophoresis apparatus was produced by VILBER LOURMAT Company (Marne-la-
5. Vallee, France ). Primers were designed using Primer 3 and synthesized by BGI Company
(Shenzhen, China). Primer sequences of Cx43 were as follows: forward: 5′-
GGCTGCTCCTCACCAACGGCC-3′; reverse: 5′-AGGTCATCAGGCCGAGGTCTG-3′.
Total RNA isolation was performed according to the instructions of RNAiso Plus; reverse
transcription was performed according to instructions of the PrimeScript RT-PCR Kit with a
total volume of 20 µl. The PCR reaction took place in a total volume of 20 µl using cDNA
0.5 µl, forward primer 0.5 µl, reverse primer 0.5 µl, Premix TAQ 12.5 µl, and RNA-free H2O
6 µl. PCR was performed at 95°C for 5 min; followed by 37 cycles of 95°C for 30 s, 58°C for
30 s, and 72°C for 35 s; and a final extension of 72°C for 10 min. Amplified products of
Cx43 were 332 bp long.
Immunohistochemistry
Two pathologists graded the specimens in a double-blind manner. Brown granules in the
cytoplasm were considered positive for Cx43, and those in the cell membrane were
considered positive for CD105; 100 tumorous and nontumorous hepatic cells were counted in
each high-power field, and 5 fields were observed for each array. The average percentages of
positive cells were then calculated. A specimen was considered Cx43+
if ≥5% of cells were
positive. The CD105 microvessel density (MVD) refers to the Weidner method [14]. A
specimen was considered VEGF+
if ≥50% of cells were positive. Cells were considered
CD105+
if they were beyond the MVD-CD105 mean line.
PCR products
We assessed the amplified RT–PCR products by electrophoresing 10 µl in a 2% agarose gel
containing ethidium bromide (0.5 mg/ml) in 0.04 M Tris-acetate and 0.001 M EDTA (TAE)
buffer at 120 V for 30 min. Gels were then developed by a UV transilluminator, and the
results were scanned by a computer.
Follow-up
Patients were followed up monthly for 3 months and every 3 months thereafter. The blood
alpha-fetoprotein (AFP) level, liver function, abdominal ultrasound or CT, and chest CT were
monitored at each follow-up. Patients who did not come in for appointments received follow-
up calls and were followed until 31 December 2011 or until death. Tumors were considered
to have recurred based on their appearance by imaging examination (abdominal ultrasound,
CT, or MRI); hepatic arteriography or biopsy was used in unclear cases. Early recurrence was
defined as recurrence within 1 year.
Statistical analysis
All data were analyzed using SPSS statistical software (ver. 13.0; SPSS Inc., Chicago, IL).
Categorical variables were compared by the χ2
test and Pearson’s correlation analysis.
Survival analysis was calculated with the Kaplan–Meier method and compared using the log-
rank test. Multivariate analyses were performed using a Cox proportional hazards model to
identify independent prognostic factors. A P value of <0.05 was considered statistically
significant.
6. Results
Survival analysis
The clinicopathologic characteristics of 234 patients with HBV-HCC are summarized in
Table 1. A total of 159 (67.9%) patients had a serum AFP level of <400 µg/l (low AFP) and
75 (32.1%) had a serum AFP level of ≥400 µg/l (high AFP). The disease-free survival (DFS)
for the low AFP and high AFP groups was 31.64 and 13.8 months, respectively (χ2
= 4.403, P
= 0.036), and the overall survival rate (OS) was 84.0 and 58.55 months, respectively (χ2
=
2.588, P = 0.108). The early recurrence rate was 27.0% (43 cases) and 49.3% (37 cases), in
the low AFP and high AFP groups respectively (χ2
= 11.253, P = 0.001).
Table 1 Clinicopathological characteristics of 234 patients with HBV-related HCC
Characteristics
Result
All Cases Cx43+
Group Cx43-
Group
Gender (male/female) 199/35 90/9 109/26
Mean age (range), years 54.2(15–82) 55.1(24–82) 55.5(15–74)
Preoperative serum AFP (<400/≥400 ng/mL) 159/75 78/21 81/54
Tumor size (≤ 5/>5 cm) 116/118 52/47 64/71
Edmondson-Steiner classification(I/II/III/ΙΙς) 25/134/11/64 15/64/4/16 10/70/7/48
Foci number(1/>1) 203/31 79/20 124/11
Liver capsule invasion(yes/no) 163/71 62/37 101/34
Satellite foci(yes/no) 31/203 13/86 18/117
TNM stage (I/II/III/ΙΙς) 137/30/63/4 58/17/23/1 79/13/40/3
Cirrhosis(yes/no) 213/21 88/11 125/10
Vascular tumor thrombosis(yes/no) 26/208 9/90 17/118
Child-Pugh class(A/B) 228/6 98/1 130/5
ALB(>35/≤35 g/L) 215/19 92/7 123/12
Tbil() 193/41 85/14 108/27
ALT(≤60/>60 U/L) 165/69 78/21 87/48
AST(≤42/>42 U/L) 157/77 74/25 83/52
1-year recurrence (yes/no) 80/154 24/75 56/79
Cx43, CD105, and VEGF expression in HBV-HCC tissues and adjacent or
cirrhotic tissues
Cx43 appeared in the cytoplasm as brown granules. The total Cx43+
rate was 42.3% (99/234)
in HCC tissues (Figure 1), 72.8% (59/81) in adjacent tissues, and 92.4% (73/79) in cirrhotic
tissues.
Figure 1 Positive expression of Cx43 in HCC tissues (400×).
The Cx43+
rate was 49.1% (78/159) in the low-AFP group and 28% (21/75) in the high-AFP
group, showing a significant difference (χ2
= 9.257, P = 0.002).
CD105 and VEGF were partly expressed in the cytoplasm as brown granules (Figures 2 and
3). The median MVD-CD105 was 19.0, and the positive CD105+
rate was 35.8% (57/159).
The VEGF+
rate was 88.7% (141/159).
Figure 2 Positive expression of CD105 in HCC tissues (400×).
7. Figure 3 Positive expression of VEGF in HCC tissues (400×).
The 38 HCC specimens preserved in –
80°C were analyzed by RT-PCR, which showed a
Cx43+
mRNA expression rate of 57.9% (22/38) (Figure 4).
Figure 4 Expression of Cx43 mRNA in HCC tissues.
Relationship among serum AFP level, Cx43 expression, and patient prognosis
Kaplan–Meier analysis (log rank test) showed that although the DFS of the Cx43+
group was
higher than that of the Cx43–
group (medians: 33.57 and 19.36 months, respectively), there
was no statistical significance. The OS of the Cx43+
group was significantly higher than that
of the Cx43–
group (P = 0.023). Cx43-
expression in patients with HCC with a low AFP level
was significantly associated with a high early recurrence rate and poor prognosis (Table 2),
unlike patients with HCC with a high AFP level. These results indicate that for patients with
HCC with a low AFP level, Cx43-
expression is a likely predictor of early recurrence and a
poor prognosis.
Table 2 Correlation of high and low serum AFP levels and Cx43 expression with
prognoses of patients with HBV-HCC who underwent radical resections
Cx43 expression n
DFS OS
Median (m) χ2
P Value Median (m) χ2
P Value
Low AFP
+ 78(23.3%) 44.00
4.963 0.026*
84.00
14.148 0.000*
- 81(34.6%) 20.12 42.74
High AFP
+ 21(9.0%) 11.45
1.721 0.190
54.03
0.012 0.912
- 54(23.1%) 16.80 61.99
Total
+ 99(42.3%) 33.57
2.440 0.118
84.00
10.657 0.001*
- 135(57.7%) 19.36 47.97
*P < 0.05
Cx43 and clinicopathological features among patients with a low AFP level
Chi-square tests showed that Cx43 expression was significantly related to histological
differentiation (P = 0.023), multiple foci (P = 0.017), vascular tumor thrombosis (P = 0.001),
and early recurrence (P = 0.006) (Table 3).
Table 3 Relationship between Cx43 expression and clinicopathological factors in
patients with HBV-HCC and low AFP levels
Cx43
χ2
P Value
- (%) + (%)
Gender Male 68(42.3%) 71(44.6%)
1.809 0.179
Female 13(8.2%) 7(4.4%)
Age > 60y 18(11.3%) 27(17.0%)
3.008 0.083
≤ 60y 63(39.6%) 51(32.1%)
Edmondson-Steiner classification I–II 51(32.1%) 66(41.5%)
9.969 0.002*
III–IV 30(18.9%) 12(7.5%)
Foci Single 64(40.3%) 72(45.3%)
5.68 0.017*
Multiple 17(10.7%) 6(3.7%)
Tumor size > 5cm 41(25.8%) 48(30.1%)
1.923 0.166
≤ 5cm 40(25.2%) 30(18.9%)
8. Liver capsule invasion No 24(15.1%) 32(20.1%)
2.262 0.133
Yes 57(35.8%) 46(28.9%)
Satellite foci No 73(45.9%) 73(45.9%)
0.636 0.425
Yes 8(5.0%) 5(3.2%)
Cirrhosis No 4(2.5%) 10(6.3%)
3.075 0.080
Yes 77(48.4%) 68(42.8%)
Vascular tumor thrombosis No 75(47.1%) 78(49.1%)
8.243 0.029*
Yes 6(3.8%) 0(0%)
Microvascular invasion No 21(27.3%) 30(40%)
5.422 0.020
Yes 18(23.4%) 8(10.3%)
Child-Pugh class A 78(49.1%) 78(49.1%)
4.102 0.246
B 3(1.8%) 0(0%)
TNM Stage I–II 79(49.7%) 78(49.1%)
1.857 0.405
III–IV 22(13.8%) 12(7.6%)
1-year recurrence No 50(31.4%) 66(41.5%)
7.544 0.006*
Yes 31(19.5%) 12(7.6%)
*P < 0.05. The HBV-HCC database of microvascular invasion was from 1 January 2008 to
31 December 2008; 87 patients entered the statistical analysis.
Expression of Cx43 protein and metastasis location with low AFP level
Among patients with HBV-HCC and a low AFP level, the Cx43+
rate in the group with
distant metastases was lower than that in patients with no metastases or liver-only metastases
(both P < 0.05) (Table 4).
Table 4 Relationship between Cx43 expression and recurrence location in patients with
HBV-HCC and serum AFP of <400 µg/l
Cx43
χ2
P Value
– +
No recurrence 329(20.1%) 37(23.3%)
1.017 0.313
Recurrence 49(30.8%) 41(25.8%)
No recurrence 32(23.9%) 37(27.6%)
0.042 0.838
Intra-hepatic recurrence 29(21.6%) 36(26.9%)
No recurrence 32(34.0%) 37(39.4%)
8.393 0.004
Extra-hepatic metastasis 20(21.3%) 5(5.3%)
Intra-hepatic recurrence 29(32.2%) 36(40%)
9.115 0.003
Extra-hepatic metastasis 20(22.2%) 5(5.6%)
Cx43 mRNA expression and early recurrence with low AFP level
Cx43 mRNA was analyzed in 38 specimens from patients with HBV-HCC and a low AFP
level, whose early recurrence rate was 26.7%; of these specimens, the Cx43 mRNA+
rate was
57.9%. The early recurrence rate was lower in the Cx43 mRNA+
group than in the Cx43
mRNA–
group (χ2
= 9.827, P = 0.002) (Table 5).
9. Table 5 Relationship between Cx43 mRNA expression and early recurrence in patients
with HBV-HCC and serum AFP of <400 µg/l
Cx43 mRNA
χ2
P Value
+ –
Non recurrence 19(50%) 6(15.8%)
9.827 0.002
Early recurrence 3(7.9%) 10(26.3%)
Relationship between Cx43 expression and VEGF and CD105 expression
Expression of MVD-CD105 and VEGF was lower in the Cx43+
group than in the Cx43–
group in HCC specimens with a low AFP level (both P < 0.05) (Table 6).
Table 6 Relationship among expressions of MVD-CD105, VEGF, and Cx43 in HCC
specimens with serum AFP of <400 µg/l
Cx43
F value P value
+ –
MVD-CD105 19.36 25.84 5.184 0.018
VEGF + mean 76.38 80.00 5.309 0.023
Expression of Cx43 protein and prognosis with a low AFP level
In patients with HBV-HCC and a low AFP level, the early recurrence rate in the Cx43+
group
was significantly lower than that in the Cx43–
group (14% and 36%, respectively; χ2
= 10.96,
P = 0.001). The median DFS in the Cx43+
group (44.0 months) was longer than that in the
Cx43–
group (20.1 months; χ2
= 4.963, P = 0.026) (Figures 5 and 6). The median OS in the
Cx43–
group (42.7 months) was significantly shorter than in the Cx43+
group (84 months; χ2
= 14.15, P = 0.000) (Figure 7). Cox regression analysis showed Cx43+
expression to be an
independent predictor of later recurrence (P = 0.042) and longer survival (P = 0.028) (Table
7).
Figure 5 Early recurrence disease-free survival curves.
Figure 6 Disease-free survival curves.
Figure 7 Overall survival curves.
Table 7 Cox regression analysis
RR 95.0% CI P Value
One-year recurrence
Histological differentiation 2.762 1.482–5.147 0.001
Cx43 expression 0.485 0.241–0.974 0.042
Vascular tumor thrombosis 6.453 2.355–17.68 0.000
Disease-free survival
Histological differentiation 1.895 1.200-2.993 0.006
Vascular tumor thrombosis 9.128 3.767-22.120 0.000
Overall survival
Histological differentiation 2.727 1.575–4.724 0.000
Vascular tumor thrombosis 15.906 5.990–42.239 0.000
Cx43 expression 0.515 0.285–0.930 0.028
10. Discussion
Although surgical techniques have improved in recent years, the high recurrence rate of HCC
after radical resection is an obstacle to survival. Previous research has shown that the 5-year
survival rate of HCC can exceed 50% after radical resection. However, the tumor recurrence
rate exceeds 70% at 5 years [3] and the small HCC recurrence rate is approximately 43.5%
[15] despite the fact that the early occurrence rate is approximately 63.5% [16]. Our research
showed an early recurrence rate of 32% and a 5-year recurrence rate of 61%.
In 1966, Loewenstein and Kanno first reported a relationship between GJs and cancer that
established a lack of electrical coupling in rat hepatomas [17]. This phenomenon was
observed in both chemically induced hepatomas and Morris and Novikoff’s transplanted
hepatomas in rats [18,19].
Today, the hypothesis associating a lack of or diminished GJs with liver cancer is still valid
[17] and continues to develop with new emerging concepts such as the possible involvement
of stem cells and their GJIC capacity in carcinogenesis [20]. A literature review [17]
described associations among how intercellular communication is involved in the
carcinogenesis process, expression of connexin (including Cx26, Cx32, and Cx43), and
particular stages of liver cancer progression by in vitro and in vivo data analyses.
Alpha-fetoprotein is synthesized by fetal hepatocytes; its seroprevalence in patients with
HCC is nearly 70%. Because of its high specificity and convenient detection, AFP is a
reliable index for screening, early diagnosis, and postoperative observation in patients with
HCC. A low AFP level is also an important reference index for the CLIP score system.
Because patients with HCC and a serum AFP level of ≥400 µg/l reportedly have significantly
shorter survival times than patients with lower serum AFP levels [21], we used a serum AFP
level of 400 µg/l as a boundary to divide patients with HCC into two groups: those with a
high AFP level and those with a low AFP level.
We found that in patients with a low AFP level, Cx43+
tumor tissues were an independent
predictor of later recurrence and a better prognosis. However, there was no relationship
between Cx43+
expression and postoperative recurrence or prognosis in patients with a high
AFP level. Therefore, Cx43+
expression is an important predictor of later recurrence and a
better prognosis in patients with a low AFP level who undergo radical hepatectomy.
Our results also showed that although Cx43 is mainly expressed in HCC cytoplasm (49.1%),
this expression is lower than in paracancerous tissue (72.8%) and cirrhosis tissue (92.4%).
We also found that Cx43 mRNA is expressed in HCC tissue using the RT-PCR method.
Ma et al. [22] investigated 61 cases of HCC and 14 cases of normal liver tissues by
immunohistochemical and in situ hybridization methods. The results indicated that the
aberrant location of Cx43 protein could be responsible for the progression of
hepatocarcinogenesis, and the mechanism may involve defects of Cx genes in post-
translational processing. Ionta et al. used Cx43 cDNA transfection to culture rabbit HCC cells
in vitro and discovered that Cx43 reduced the multiplication capacity of these cells and
restrained cancer cell growth [23]. Ogawa et al. established six rat HCC cell lines that
exhibited different metastatic potentials after inoculation into the tail veins of nude mice and
transfection of an siRNA targeting Cx43 (as shown by cDNA array analysis), indicating that
suppression of Cx43 expression in tumor cells reduced in vitro migration and invasion
capacity and in vivo metastatic ability [24].
11. Our results also showed that Cx43 expression in HCC tissue is inversely related to invasion
and metastasis, expression of VEGF and CD105, and vascular tumor thrombosis. Cx43 is an
independent predictor of later recurrence and longer OS after HCC radical hepatectomy. The
RT-PCR results also showed that expression of Cx43 mRNA is related to later recurrence.
CD105-MVD reflects new vessel growth in HCC tissue and is an independent predictor of
recurrence, metastasis, and vessel invasion in postoperative patients with HCC [25]. VEGF
can substantially accelerate division and growth of vascular endothelial cells and
angiogenesis. High VEGF levels can promote plasma protein exosmosis to induce fibrin
deposition and new vessel generation, allowing invasion and metastasis; patients with HCC
and higher VEFG expression in serum and HCC tissue have a poorer prognosis [9,26].
Immunohistochemistry results showed higher expression of CD105 and VEGF in patients
with lower Cx43 levels. The reason may be that impaired GJIC function is closely related to
early tumor occurrence, invasion, and metastasis [17]. Cx43 expression in HCC tissue can
improve intercellular GJIC and restrain expression of the tumor accelerator angiogenesis
factor, thus reducing recurrence and metastasis. This result indicates that Cx43 expression in
HCC tissue is inversely related to important factors of postoperative HCC recurrence, such as
tumor differentiation (P = 0.002) and vascular tumor thrombosis (P = 0.029), showing that
Cx43 affects HCC recurrence and metastasis.
The present results indicate that patients with Cx43+
HBV-HCC have a longer OS than do
patients with Cx43–
HBV-HCC. In particular, patients with Cx43+
HBV-HCC have better 1-
year DFS and OS than do those with Cx43–
HBV-HCC and low serum AFP levels.
Conclusion
This study demonstrated that Cx43+
expression in HBV-HCC tissue is a predictor of lower
early recurrence rates and better prognosis in patients with low serum AFP levels and could
be significant in terms of improving individualized treatments.
Abbreviations
HCC, Hepatocellular carcinoma; Cx43, Connexin-43; GJs, Gap junctions; GJIC, Gap
junction intercellular communication; HBV, Hepatitis B virus; VEGF, Vascular endothelial
growth factor; RT-PCR, Reverse transcription polymerase chain reaction; AFP, Alpha-
fetoprotein; MVD, Microvessel density; CT, Computed tomography; MRI, Magnetic
resonance imaging; ALB, Serum albumin; Tbil, Total bilirubin; ALT, Alanine transaminase;
AST, Glutamic-oxalacetic transaminase; DFS, Disease-free survival; OS, Overall survival;
HBV-HCC, Hepatitis B-related hepatocellular carcinoma; High AFP, Serum AFP of ≥400
µg/l; Low AFP, Serum AFP of <400 µg/l.
Competing interests
The authors declare that they have no competing interests.
12. Authors’ contributions
ZSW and LQW participated in the design of the experiments, data interpretation, and
manuscript preparation. XY and CG contributed equally to this work. They performed the
experiments, including immunohistochemistry and RT-PCR experiments; analyzed the data;
and participated in the writing of the manuscript. YJL and RYY guided the
immunohistochemistry and RT-PCR experiments and participated in the design of the
experiments. All authors read and approved the final manuscript.
Acknowledgements
We thank the Department of Pathology of Qingdao Municipal Hospital, who provided
technique support of the tissue microarray.
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