Cisplatin / Ki-67 Cancer Research Results

Cisplatin, Cisplatin: Click to Expand ⟱
Features:
Cisplatin is a chemotherapy medication used to treat various types of cancer. It is a platinum-based drug that works by interfering with the DNA of cancer cells, preventing them from reproducing and ultimately leading to cell death.
Cisplatin (cis-diamminedichloroplatinum II; CDDP) is a platinum-based chemotherapeutic agent that forms covalent DNA crosslinks, primarily intrastrand adducts at adjacent guanine bases. These distort DNA structure, block replication and transcription, and activate DNA damage response pathways (ATM/ATR → p53), leading to cell-cycle arrest and apoptosis. Secondary mechanisms include ROS generation, stress MAPK activation, and modulation of NF-κB. Clinical resistance frequently involves enhanced DNA repair (ERCC1/NER), altered drug transport (CTR1, ATP7A/B), and increased antioxidant defenses. Major toxicities include nephrotoxicity, ototoxicity, and peripheral neuropathy.

Rank Pathway / Axis Cancer / Tumor Context Normal Tissue Context TSF Primary Effect Notes / Interpretation
1 DNA crosslink formation (intrastrand adducts) DNA adducts ↑; replication block ↑ Normal dividing cells also affected P, R, G Direct DNA cytotoxicity Cisplatin forms covalent intrastrand crosslinks (primarily at adjacent guanines), distorting DNA and blocking replication and transcription.
2 DNA damage response (ATM / ATR → p53) Checkpoint activation ↑; p53 signaling ↑ ↔ (toxicity in proliferating tissues) R, G Damage signaling cascade DNA distortion activates ATM/ATR pathways leading to p53-mediated cell-cycle arrest and apoptosis.
3 Intrinsic apoptosis (mitochondrial pathway) Bax ↑; Bcl-2 ↓; caspase-9/3 ↑ Nephrotoxicity & ototoxicity risk G Execution of cell death Persistent DNA damage triggers mitochondrial outer membrane permeabilization and caspase activation.
4 Cell-cycle arrest (G2/M emphasis) G2/M arrest ↑ ↔ G Cytostasis → apoptosis Cells accumulate in G2/M phase due to unrepaired DNA lesions.
5 ROS generation / oxidative stress ROS ↑ (secondary mechanism) Oxidative injury ↑ (kidney, cochlea) R, G Stress amplification Cisplatin increases mitochondrial ROS and oxidative stress, contributing to cytotoxicity and organ toxicity.
6 MAPK signaling (JNK / p38 activation) Stress MAPK activation ↑ ↔ R, G Stress-response signaling JNK and p38 activation contribute to apoptosis and stress signaling.
7 NF-κB activation (resistance axis) NF-κB ↑ may promote survival ↔ R, G Resistance modulation NF-κB activation can reduce sensitivity; inhibition enhances cytotoxicity in some models.
8 DNA repair pathways (NER / ERCC1) NER ↑ → resistance — G Resistance determinant Nucleotide excision repair (ERCC1) removes platinum adducts; high ERCC1 correlates with resistance.
9 Drug transport (CTR1 uptake; ATP7A/B efflux) CTR1 ↓ or ATP7A/B ↑ → resistance — G Exposure constraint Copper transporters influence intracellular cisplatin accumulation and resistance.
10 Clinical toxicity profile — Nephrotoxicity, ototoxicity, neurotoxicity — Translation constraint Major dose-limiting toxicities arise from DNA damage and oxidative stress in normal tissues.

Time-Scale Flag (TSF): P / R / G

  • P: 0–30 min (DNA aquation and initial adduct formation)
  • R: 30 min–3 hr (checkpoint activation / stress signaling)
  • G: >3 hr (apoptosis, phenotype outcomes, resistance development)
Ki-67, Ki-67 protein: Click to Expand ⟱
Source:
Type: proliferation marker
A high Ki-67 proliferation index means many cells are dividing quickly and that the cancer is likely to grow and spread.
Markers of proliferation index (Ki-67)

• Ki-67 serves primarily as a proliferation marker: higher levels are generally indicative of aggressive disease and poorer outcomes across many cancer types.
• While Ki-67 itself is not considered a driver of tumorigenesis, its expression mirrors the high proliferative activity associated with protumoral behavior.
• It is widely used in clinical practice to aid in tumor grading, prognostication, and treatment planning.
Scientific Papers found: Click to Expand⟱
584- Api,  Cisplatin,    Apigenin potentiates the antitumor activity of 5-FU on solid Ehrlich carcinoma: Crosstalk between apoptotic and JNK-mediated autophagic cell death platforms
- in-vivo, Var, NA
Beclin-1↑, Casp3↑, Casp9↑, JNK↑, Mcl-1↓, Ki-67↓,
801- GAR,  Cisplatin,    Garcinol sensitizes human head and neck carcinoma to cisplatin in a xenograft mouse model despite downregulation of proliferative biomarkers
- in-vivo, HNSCC, NA
Apoptosis↑, cycD1/CCND1↓, Bcl-2↓, survivin↓, VEGF↓, TumCG↓, Ki-67↓, CD31↓,

Showing Research Papers: 1 to 2 of 2

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 2

Pathway results for Effect on Cancer / Diseased Cells:


Cell Death ⓘ

Apoptosis↑, 1,   Bcl-2↓, 1,   Casp3↑, 1,   Casp9↑, 1,   JNK↑, 1,   Mcl-1↓, 1,   survivin↓, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↑, 1,  

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

TumCG↓, 1,  

Migration ⓘ

CD31↓, 1,   Ki-67↓, 2,  

Angiogenesis & Vasculature ⓘ

VEGF↓, 1,  

Clinical Biomarkers ⓘ

Ki-67↓, 2,  
Total Targets: 14

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: Ki-67, Ki-67 protein
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:197  Target#:425  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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