Hepatocellular Carcinoma

Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world.

Cytological Appearance

Diagnosis of Hepatocellular Carcinomas

Prognosis in patients with hepatocellular carcinoma is determined by the tumor stage and by the functional status of the liver.

Primary symptoms of hepatocellular carcinoma are those of a hepatic mass. In most cases, rapid deterioration of hepatic function may be the only physical clue to the presence of a neoplasm.

Abnormal Liver function tests: increased serum bilirubin levels elevated serum alkaline phosphatase elevated g-glutamyl transpeptidase levels diminished serum albumin concentration progressive increase of elevated serum-alpha fetoprotein (AFP)

Radiological Tests: Diagnosis is often made with a combination of abdominal ultrasound and CT, angiography, and biopsy.

Screening of High Risk Populations: Includes periodic ultrasound examinations and serum fetoprotein levels.

Current Treatments For Hepatocellular Carcinoma

Current Treatments for Hepatocellular Carcinoma:

1. Cryosurgery to freeze and kill the cancerous tumor cells.

2. Injection of ethanol directly into tumor areas.

3. Focused Radio-wave ablation of tumor areas.

4. Regional and/or Systemic chemotherapy.

5. Radiation therapy coupled with medications that induce susceptibility of cells to

radiation.

6. Resectional surgery with or without chemotherapy and radiation therapy.

7. Liver Transplantation.

Hepatitis B virus

* As cancers progresses, cells become less differentiated
& more heterogeneous with respect to the mutations they carry.

*Cancers have at least one mutation to a proto-oncogene (yielding an oncogene)
& at least one to a tumour suppressor gene, allowing the cancer to proliferate.

*The range of mutations and different types of cancers have led to a variety of new potential treatments:

The Much talked about
Infamous P21 of Chromosome 5:

p21 Gene location on Chromosome 5.

Protein product of gene transcription is composed of 1047 amino acids.

Implicated as a major component in cell cycle regulation.

GTP-binding protein having GTPase activity and regulated by bound GDP/GTP.

ALIAS:

Human GTPase-activating protein ras p21 (RASA) mRNA

Ras GTPase-activating protein 1

(GTPase-activating protein) (GAP)

(Ras p21 protein activator)

(p120GAP)

(RasGAP)

GTPASE-ACTIVATING PROTEIN

P21 Cell Cycle Arrest

P21 Inhibits Thymidine Incorporation into DNA in Hepatocellular Carcinoma and Inhibits Tumor Cell Proliferation through Inhibition of Cyclin Dependent Kinases

Repression of the p21waf1 promoter via a p53-independent pathway:
Deletional Analysis of the p21waf1 promoter

Repression of the p21waf1 promoter via a p53-independent pathway:
Repression of p21waf1 transcription by HBx in
p53 -/- cells

P21waf1 full length and sequence mutated variants of the promoter constructs were developed
using wild-type p21P 93-S sequences identical to the sequences for the p21 promoter with the exception
that each mutant construct contains nonsense nucleotide sequences in place of the original 5’ promoter sequence at different sections of the p21 promoter sequence. The mutated promoter sequences of the p21 constructs were incorporated 5’ of the luciferase expression indicator gene and cotransfected with either an empty plasmid vector (pCl-neo) or an HBx expressing plasmid vector (pCl-neo-Hbx) into pNIH 3T3 cells.
Mutations were examined within the 60 bp promoter sequence between bp -93 and bp -34.

The basal luciferase activity of the p21P 93-S construct was designated to be 100% and each luciferase activity measured from mutants without the HBx-expressing plasmid vector was determined to be related comparatively to the basal activity reduction caused by the specific mutation alone.

Luciferase activity was then analyzed to determine specific repression of p21 induced by HBx interaction with specific response elements in the p21waf1 promoter.

Identification of HBx-Responsive Elements in the p21waf1 Promoter

SP1-mediated Repression of p21waf1 Transcription by HBx Hepatitis B Viral Protein

Can A Kissing Disease Cure Cancer?

HEPATOCELLULAR CARCINOMA CURES USING EPSTEIN-BARR VIRUS-BASED
PLASMID VECTORS?

Epstein-Barr or Human Herpesvirus 4
normally integrates into the host genome and causes persistent infections with long term side effects .
Epstein-Barr deaths
tied to faulty protein: A rare, deadly complication of Epstein-Barr virus is caused by a defective immune system protein. Epstein-Barr
associated with Burkitt’s Lymphoma.

Just How Dangerous is Epstein-Barr Virus?

Epstein-Barr Virus Persistence in DNA and Immune System Avoidance of Latently Infected Cells

Questions

How can Lux AB be used to in Recombinant Research work to measure the expression levels of a gene?

Discuss why Virus-Based Plasmids might provide an effective system for gene delivery in medical therapies and discuss the potential risks of using Virus-Based Plasmids for gene delivery in medical treatments.

Why is Epstein-Barr (Herpes gamma virus) considered a good candidate virus for gene delivery in gene therapy.

How does infection with the Hepatitis B Virus affect cell cycle arrest by p21 to induce the development of Hepatocellular Carcinoma?