Oncogenic Insulin-like Growth Factor-1 Receptor (IGF-1R) As a Promising Targeted-molecule for HCC Therapy | Chapter 1 | New Visions in Medicine and Medical Science Vol. 9

 

The present study aimed to investigate the clinicopathological features of insulin-like growth factor-1 receptor (IGF-1R) or P-glycoprotein (P-gp) expression in tissues and sera of hepatocellular carcinoma (HCC) patients, further analyze IGF-1R on effects of biological behaviors of HepG2 cells and synergistic role with anti-cancer drugs on reversal MDR of HCC. In HCC, there was an overexpression of the IGF-1R. The connection between IGF-1R activation and the advancement of HCC is still unknown, though. In this work, we looked into how the biological characteristics of HCC cells were affected by IGF-1R editing. The expressions of IGF-1R and P-gp in HCC and their distal non-cancerous tissues (Non-Ca) were analyzed by immunohistochemistry. IGF-1R was edited with CRISPR/Cas9 system, screened specific sgRNAs, and then transfected into HepG2 cells. CCK-8 and scratch wound test detected cell proliferation, migration, invasion, and transwell assays, respectively. Alterations of IGF-1R and P-gp were confirmed by Western blotting. Alterations of anti-cancer drug IC50 values were analyzed at the cell level. The incidences of IGF-1R (93.6%) or P-gp (88.2%) were significantly higher (P<0.001) in the HCC group than those (36.6% in IGF-1R or 26.9% in P-gp) in the Non-Ca group. There was a positive correlation between high IGF-1R and P-gp expression, and they were associated with HBV infection and vascular invasion of HCC. Abnormal levels of serum IGF-1R and P-gp were confirmed and associated with HCC progression. Biological feature alterations of HCC cells transfected with specific sgRNA showed IGF-1R expression down-regulation, cell proliferation inhibition, cell invasion or migration potential decreasing, and enhancing susceptibility of HepG2 cells to anti-cancer drugs. In this study, the specific sgRNA plus anti-tumor drugs had higher inhibitory effects on HCC cells, and the drug IC50 values were significantly decreased with inhibiting cell proliferation of HCC in the sgRNA group, indicating that HCC cells transfected with sgRNA could be more sensitive to anti-cancer drugs via inhibiting the NF-kappa B pathway. These data indicated that the edited oncogenic IGF-1R was useful to inhibit biological behaviors of HCC cells and IGF-1R should be a promising targeted-molecule for HCC therapy.

 

 

Author(s) Details:-

 

Min Yao
Research Center of Clinical Medicine, Affiliated Hospital of Nantong University & Department of Medical Immunology, Medical College of Nantong University, Nantong 226001, Jiangsu, China.

 

Wenli Sai
Research Center of Clinical Medicine, Affiliated Hospital of Nantong University & Department of Medical Immunology, Medical College of Nantong University, Nantong 226001, Jiangsu, China.

 

Chunxiu Sha
Research Center of Clinical Medicine, Affiliated Hospital of Nantong University & Department of Medical Immunology, Medical College of Nantong University, Nantong 226001, Jiangsu, China.

 

Min Xu
Research Center of Clinical Medicine, Affiliated Hospital of Nantong University & Department of Medical Immunology, Medical College of Nantong University, Nantong 226001, Jiangsu, China.

 

Rongfei Fang
Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong 226001, China.

 

Li Wang
Research Center for Intelligent Information Technology, Nantong University, Nantong 226019, China.

 

Qun Xie
Department of Infectious Diseases, Haian People’s Hospital, Haian 226600, Jiangsu, China.

 

Dengfu Yao
Research Center of Clinical Medicine, Affiliated Hospital of Nantong University & Department of Medical Immunology, Medical College of Nantong University, Nantong 226001, Jiangsu, China.

 

Please see the link here:-  https://doi.org/10.9734/bpi/nvmms/v9/11781F

Serum Zinc Levels as a Potential Predictive Marker for Hepatic Carcinoma: A Meta-Analysis | Chapter 6 | New Visions in Medicine and Medical Science Vol. 1

Introduction: Zinc, a crucial trace element in the human body, plays a pivotal role in various physiological processes due to its involvement in enzyme structure and function. Its significance in health and disease, particularly in liver disorders and cancer, has gained attention. However, inconsistencies exist in literature regarding zinc levels and their association with hepatic carcinomas.

Methods: A meta-analysis was conducted following PRISMA guidelines to analyze the relationship between serum zinc levels and hepatic cancer. Data were extracted from epidemiological studies retrieved from NLM-PubMed databases. Inclusion criteria involved studies assessing blood zinc levels' association with liver cancer and providing mean values with standard deviation.

Results: Seven eligible studies were included, showing significant heterogeneity. The combined average zinc level in hepatic carcinoma patients was 74.06 µg/dL (95% CI: 61.0 - 87.06), indicating a substantial deviation from normal levels. Publication bias was observed.

Conclusion: The meta-analysis underscores the importance of zinc in liver cancer risk assessment and disease progression. Lower than expected pooled zinc levels in hepatic carcinoma patients highlight its potential as a predictive marker for liver malignancies and chronic liver diseases. Further research is warranted to elucidate zinc's precise role and clinical implications in hepatic carcinogenesis.

 

Author(s) Details:

Abhishek Bansal,
Department of Biochemistry, Pt. B D Sharma PGIMS, Rohtak, HR, India.

Praveen Prashant,
Department of Biochemistry, Pt. B D Sharma PGIMS, Rohtak, HR, India.

Pragya Dixit,
ESI Health Care Haryana, ESI Hospital Panipat, HR, India.

Sonia Vashist,
Department of Dermatology, Tripti Hospital, Rohak, HR, India.

Please see the link here: https://stm.bookpi.org/NVMMS-V1/article/view/13655

Oncogenic Wnt3a Signaling as a Specific Molecular Marker for Hepatocellular Carcinoma | Chapter 2 | Advancement and New Understanding in Medical Science Vol. 7

Hepatocellular carcinoma (HCC) is still one of the most common and rapidly fatal malignancies worldwide with a multi-factorial, multi-step, complex process, and poor prognosis. Carcinogenesis of HCC is a multi-factor, multi-step and complex process. Early discovery and effective therapy of HCC are of utmost importance. Recent studies demonstrated that Wnt/β-catenin pathway play importance roles in occurrence and development of HCC including hepatocytes malignant trans-formation, metastasis, chemo-resistance and liver cancer stem cells. Oncogenic wingless-type MMTV integration site family member 3a (Wnt3a) signaling is a promising biomarker in diagnosis and prognosis for HCC. The positive Wnt3a with brown staining particles was mainly distributed in cytosol and membrane of hepatocytes in cancerous tissues and no or lower expression in their surrounding tissues. This review presents current data on mechanisms of hepatocarcino-genesis involving participation of the Wnt canonical pathway, and focuses on the Wnt3a expression in HCC progression and its clinical application. Oncogenic Wnt3a has been confirmed abnormal expression in hepatocarcinogenesis model.

Author(s) Details:

Min Yao,
Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China and Department of Immunology, Medical School of Nantong University, Nantong 226001, Jiangsu, China.

Rongfei Fang,
Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China.

Min Xu,
Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China.

Wenli Sai,
Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China.

Qun Xie,
Department of Infective Diseases, Haian People’s Hospital, Haian 226500, Jiangsu, China.

Dengfu Yao,
Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China.

Please see the link here: https://stm.bookpi.org/ANUMS-V7/article/view/13418

Availability of 5-fluorouracil and High-concentration Cisplatin with Short-term Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma | Chapter 9 | Current Innovations in Medicine and Medical Science vol. 1

 The purpose of this study was to evaluate the effectiveness and utility of 5-fluorouracil (5-FU) and high-concentration cisplatin in advanced hepatocellular carcinoma (HCC) patients receiving short-term (3-day FPL) hepatic arterial infusion chemotherapy.

30 patients with advanced HCC that was unresectable were included in the study. A fine-powder formulation of cisplatin in suspended, pre-warmed lipiodol on Day 2 and hepatic arterial infusion chemotherapy with 5-FU on Days 1-3 were administered to the patients via the implanted port system every 4 to 10 weeks. CT was utilised to evaluate the tumour response one month later. The prognosis is often bad for patients with advanced HCC. The study's findings showed that every patient had signs of portal vein invasion (Vp2-4). Seven patients had stable disease, eight patients had partial responses, and four patients had complete responses (SD). Overall survival (OS) and progression-free survival (PFS) had medians of 198 days and 452 days, respectively. The successful disease control group (CR, PR, and SD) had an OS that was considerably longer than the disease progression group (P .005). Three-day FPL demonstrated efficacy and tolerance in patients with advanced HCC due to its rapid delivery than conventional FP therapy. Thus, recurring 3-day FPL, which looks to be efficient, appears to enhance the prognosis and quality of life of patients with advanced HCC.

Author(s) Details:

Yutaka Yata,
Department of Hepatology, Osaka Metropolitan University, Japan and  Department of Gastroenterology, Hanwa Memorial Hospital, Japan.

Please see the link here: https://stm.bookpi.org/CIMMS-V1/article/view/8108

The Importance of Liver Fatty Acid-Binding Protein Downregulation in Hepatocellular Carcinoma| Chapter 13 | Highlights on Medicine and Medical Science Vol. 9

 The goal of this study was to see how significant it was in hepatocellular carcinoma for the expression of liver fatty acidbinding protein (L-FABP) to be downregulated (HCC). Methods: On tissue microarrays from 146 cases of HCC, immunohistochemical labelling for L-FABP was conducted. Further immunohistochemical staining was done on a representative whole-tissue section for each L-FABP-negative HCC to validate the downregulation of L-FABP expression and examine intratumoral heterogeneity of the staining pattern. Clinical data was acquired from the clinical files and histological slides were inspected. Immunohistochemical staining for cytokerati on tissue microarrays There was also a test for serum amyloid A (SAA). Clinicopathological characteristics of L-FABP-negative and L-FABP-positive HCC patients were compared. In addition, real-time reverse transcription polymerase chain reaction was used to examine L-FABP and GS gene expression in HCC and cholangiocarcinoma (CC) cell lines. For L-FABP-negative HCC cases, mutation analysis of HNF1A (encoding hepatocyte nuclear factor 1 (HNF1)) was done. Sixteen of the 146 HCC patients (10.9 percent) were negative for L-FABP. When we looked at the relationship between L-FABP downregulation and tumour size, we found that most cases of smaller HCC (less than 2 cm in diameter) had localised downregulation, while most cases of bigger HCC (more than 2 cm in diameter) had diffuse downregulation. The connection (P = 0.036) was statistically significant. The L-FABP-negative area commonly resembled a "nodule-in-nodule" look when the HCC was smaller. Tumor differentiation was much lower, and the frequency of intratumoral inflammation was significantly lower in L-FABP-negative cases than in L-FABP-positive cases in small HCC cases. Cases with FABP positivity (P = 0.032 and 0.009, respectively). L-FABP-negative instances of small HCC had a considerably greater frequency of -catenin and GS staining than L-FABP-positive cases of small HCC (P = 0.009 and P = 0.000, respectively). Four of the six HCC cell lines studied had increased L-FABP expression, whereas the remaining two had lower or no L-FABP expression. A mutation in exon 4 of HNF1A was found in two of the 16 L-FABP-negative HCC cases. Conclusion: L-FABP downregulation occurs in smaller HCCs due to phenotypic changes as the tumour progresses. Furthermore, this downregulation was linked to tumour differentiation and inflammation within the tumour.

Author(s) Details

Masafumi Inoue
Department of Pathology, Toranomon Hospital, Tokyo 105-8470, Japan.

Yoshihisa Takahashi
Department of Pathology, Teikyo University School of Medicine, Tokyo 173-8605, Japan.

Takeshi Fujii
Department of Pathology, Toranomon Hospital, Tokyo 105-8470, Japan.

Masanobu Kitagawa
Department of Comprehensive Pathology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.

Toshio Fukusato
Department of Pathology, Teikyo University School of Medicine, Tokyo 173-8605, Japan.


View Book :- https://stm.bookpi.org/HMMS-V9/article/view/2247

Potential Targets for Prevention and Treatment of Nonalcoholic Fatty Liver Disease in Adults: A Review | Chapter 6 | Technological Innovation in Pharmaceutical Research Vol. 8

 NAFLD (nonalcoholic fatty liver disease) is a common illness that can develop to serious liver problems such hepatic fibrosis and hepatocellular cancer. Sedentary behaviour and a high-calorie diet are the most typical causes. There is currently no FDA-approved medicine to treat NAFLD in the United States, leaving only dietary changes, increased physical activity, exercise, and antioxidants as possibilities. The Drug Controller General of India (DGCI) authorised Saroglitazar Mg as a new drug application (NDA) to treat NAFLD in India in December 2020. The pathogenesis, diagnostic procedures, and prospective targets for NAFLD prevention and treatment are all detailed in this review.

Author (s) Details

Jarnail Singh Braich
Department of Pharmacology, Pt BD Sharma Postgraduate Institute of Medical Sciences, Rohtak-124001 (IN), India.

View Book :- https://stm.bookpi.org/TIPR-V8/article/view/2209

Advanced Studies on Protein Induced by Vitamin K Absence or Antagonist II-Producing Gastric Cancer | Chapter 15 | Highlights on Medicine and Medical Science Vol. 8

 PIVKA-II (protein induced by vitamin K deficiency or antagonist II) is a potential hepatocellular carcinoma (HCC) specific marker, however it can also be produced by a small number of stomach cancers. So far, 16 cases of PIVKA-II-producing stomach cancer have been reported, two of which were reported by us and all of which were discovered in Japan. Serum alpha-fetoprotein (AFP) levels are almost always high as well. In around 80% of cases, liver metastases is discovered, and portal vein tumour thrombus is discovered in about 20% of cases. It's not always easy to distinguish between a metastatic liver tumour and HCC. On the surface, almost all of the patients appear to be advanced stomach cancer. A hepatoid pattern, as well as a moderately to poorly differentiated adenocarcinoma component, is seen in many instances. To validate the formation of PIVKA-II and AFP, immunohistochemical staining is usually utilised. Treatment and prognosis are influenced by the existence of liver metastasis, and patients with liver metastasis have a poor prognosis. During hepatocellular metaplasia, tumour cells may produce PIVKA-II.

Author (s) Details

Yoshihisa Takahashi
Department of Pathology, Teikyo University School of Medicine, Tokyo 173-8605, Japan.

Tohru Inoue
Department of Pathology, Tokyo Kousei-Nenkin Hospital, Tokyo 162-8543, Japan.

Toshio Fukusato
Department of Pathology, Teikyo University School of Medicine, Tokyo 173-8605, Japan.

View Book :- https://stm.bookpi.org/HMMS-V8/article/view/2175

Research on Identification of Diagnostic Biomarker for Hepatocellular Carcinoma: A Proteomic Approach | Chapter 8 | Research Trends and Challenges in Medical Science Vol.3

 Hepatocellular carcinoma (HCC), a slow multistep process eventually starts from longterminflammation to fibrosis and leads to malignancy. These variations cause several genes disrupted that play role many signaling pathways involved in HCC. Early diagnosis and treatment of hepatocarcinogenesis depend on efficient biomarker discovery. To date, only two specific markers of HCC are identified, AFP and AFP-L3, but assessment and validation of these markers are still left in large cohorts of patients. Proteomic approach aids to develop new promising biomarker for diagnosis liver cancer at early stage. In current chapter early stage biomarker (cAMP-dependent protein kinase inhibitor alpha (PKIA)) have been identified using one-dimensional electrophoresis (1DE) and 2DE followed by matrix-assisted laser desorption and ionization time-of-flight mass spectrometry. This chapter alsohypothesized that PKIA is useful for detection of HCC at initial stage.

Author(s) Details

 Dr. Sandhya Hora
Department of Biotechnology, HIMT Group of Institutions, Greater Noida, Uttar Pradesh, India and Proteomic and Translational Research Lab, Centre for Medical Biotechnology, Amity Institute of Biotechnology, Amity University, Noida, Uttar Pradesh, India.

Dr. Savita Mishra
Proteomic and Translational Research Lab, Centre for Medical Biotechnology, Amity Institute of Biotechnology, Amity University, Noida, Uttar Pradesh, India.

Dr. Deepshikha Pande Katare
Centre for Medical Biotechnology, Amity Institute of Biotechnology, Amity University, Uttar Pradesh, India.

View Book:- http://bp.bookpi.org/index.php/bpi/catalog/book/211