Molecular Medicine: Inflammation, Wound Healing, Cancer, DNA Repair & Therapy (Vocabulary Flashcards)

A comprehensive set of vocabulary flashcards covering wound healing, inflammation, cancer biology, DNA repair, epigenetics, infectious cancer, and therapeutic concepts drawn from the lecture notes.

HIP-R

Mnemonic for the four wound-healing phases: Haemostasis, Inflammation, Proliferation, Remodelling.

Haemostasis

Wound-healing phase 0–20 min: vasoconstriction, platelet plug formation, coagulation to form a fibrin clot.

Inflammation

Wound-healing phase 0–6 days: neutrophils (0–48h) followed by macrophages (48–96h) with cytokines IL-1, TNF-α, IL-6, NO, prostaglandins.

Proliferation

Wound-healing phase 4–14 days: fibroplasia (fibroblasts → ECM Type III collagen), VEGF-driven angiogenesis, re-epithelialization (keratinocyte migration; EMT to MET).

Remodelling

Wound-healing phase 8 days–1 year: Type III collagen replaced by stronger Type I; MMPs remodel ECM; end when Type I:III ~4:1.

Neutrophils

First responders in inflammation; perform phagocytosis; typical window 0–48 hours.

Macrophages M1

Inflammatory macrophages that promote debris clearance and host defense.

Macrophages M2

Healing macrophages that promote tissue repair and regeneration.

Cytokines IL-1, TNF-α, IL-6

Key inflammatory mediators driving vasodilation, leukocyte recruitment, and fever/acute phase responses.

Nitric oxide (NO)

Cytokine/vasodilator involved in inflammation and antimicrobial activity.

Prostaglandins

Inflammatory mediators produced during the inflammatory response; contribute to vasodilation and pain.

Fibroplasia

Proliferation of fibroblasts producing extracellular matrix during wound repair.

ECM Type III collagen

Initial collagen in wound repair; later replaced by Type I collagen during remodelling.

Angiogenesis

New blood vessel formation; VEGF-driven process during wound healing and tumor growth.

VEGF

Vascular Endothelial Growth Factor; central driver of angiogenesis.

Re-epithelialization

Migration of keratinocytes to restore epidermal layer; may involve EMT/MET transitions.

EMT

Epithelial-to-mesenchymal transition; increases motility and invasiveness.

MET

Mesenchymal-to-epithelial transition; re-establishment of epithelial traits.

MMPs

Matrix metalloproteinases; degrade ECM during remodeling; TIMPs inhibit MMPs.

PRISH

Signs of inflammation: Pain, Redness, Immobility, Swelling, Heat.

PAMPs

Pathogen-associated molecular patterns detected by pattern-recognition receptors (TLRs).

DAMPs

Damage-associated molecular patterns detected by receptors (NLRs); trigger inflammation.

TLRs

Toll-like receptors that recognize PAMPs and activate innate immunity.

NLRs

Nod-like receptors that recognize DAMPs and initiate inflammatory responses.

VEC-CD-P

Sequence mnemonic for inflammation: Vasodilation, Edema, Chemotaxis, Cytokine amplification, Destruction, Proliferation prep.

Vasodilation

Early inflammatory response increasing blood flow to the site.

Edema (permeability ↑)

Fluid leakage into tissues due to increased vascular permeability.

Chemotaxis

Recruitment of neutrophils and other immune cells via cytokines.

Cytokine amplification

Amplified signaling (e.g., IL-1, IL-6, TNF) driving the inflammatory response.

Destruction (phagocytosis, NETs)

Removal of pathogens by phagocytes; neutrophil extracellular traps (NETs) may form.

Proliferation prep (M2 macrophages, growth factors)

Preparation of tissue for repair; M2 macrophages secrete pro-regenerative signals.

Mast cells

Cells releasing histamine and prostaglandins to promote inflammation.

Histamine

Vasoactive mediator released by mast cells; promotes vasodilation and permeability.

Dendritic cells

Antigen-presenting cells that activate T cells and bridge innate/adaptive immunity.

Neutrophils (first responders)

Rapid responders in acute inflammation; primary phagocytes.

Macrophages (M1/M2)

M1: inflammatory; M2: healing/regeneration macrophages.

Complement C3a/C5a

Anaphylatoxins that promote inflammation and recruit immune cells.

Complement C3b

Opsonin that enhances phagocytosis of pathogens.

MAC (C5b-C9)

Membrane attack complex; forms pore in target cell membranes leading to lysis.

Complement system

A system of plasma proteins that enhances inflammation and immunity via opsonization, chemotaxis, and lysis.

Inflammation sequence (VEC-CD-P) – activators

Activators include VEGF, TNFα, PDGF, TGFβ promoting angiogenesis and repair.

Angiogenesis in cancer: angiogenic switch

Tumors shift from dormant to vascularized by releasing VEGF (often via MMP activity).

Tumor vasculature abnormalities

Chaotic, leaky vessels with reduced pericytes and abnormal basement membranes.

Warburg effect

Cancer cells preferentially use glycolysis for energy even in the presence of oxygen.

PET scans with FDG

Imaging using 18F-FDG to detect high glucose uptake by tumors.

Immune surveillance

Theory that immune system detects/eliminates transformed cells; supported by cancers in immunosuppressed.

Tumor antigens: TSA vs TAA

TSA: tumor-specific antigens; TAA: overexpressed/aberrant self-antigens.

CD8+ T cells

Cytotoxic T cells that kill target cells via FASL or perforin/granzyme.

CD4+ T cells

Helper T cells secreting cytokines (IL-2, IFN-γ) and activating other immune cells.

NK cells

Natural killer cells that kill cells with low MHCI or stress ligands.

MHC I and MHC II

MHC I presents to CD8+ T cells; MHC II presents to CD4+ T cells.

Immune evasion (tumors)

Strategies include reduced MHCI, decreased stress receptor expression, anti-apoptosis, soluble FASL, and complement inhibitors.

Invasion & metastasis

Breach of basement membrane; routes include lymphatic, hematogenous, transcoelomic, implantation.

Metastatic cascade steps

Detachment, ECM adhesion, protease secretion, intravasation, survival, extravasation, colonization.

EMT in cancer

Epithelial cells acquire mesenchymal traits, gaining motility and invasiveness.

HIF-1α

Hypoxia-inducible factor; stabilized in hypoxia and upregulates VEGF.

Angiogenesis in cancer – regulators

Activators: VEGF, TNFα, PDGF, TGFβ; Inhibitors: Thrombospondin, Endostatin, TIMPs, IL-4.

Cancer stem cells

Self-renewing, tumor-initiating subpopulation linked to EMT and metastasis.

SASP

Senescence-associated secretory phenotype; SASP factors recruit immune cells and remodel ECM.

Telomere shortening (Hayflick limit)

Limit on cell divisions leading to senescence unless telomerase reactivates.

Immortalisation

Escape from senescence via loss of p53/Rb or activation of telomerase.

Telomerase

Ribonucleoprotein that maintains telomeres; promotes replicative immortality.

Crisis in immortalization

Severe telomere shortening causes genome instability; cells may die or reactivate telomerase.

DNA damage and repair overview

Cells suffer numerous DNA lesions daily; unrepaired damage leads to senescence, apoptosis, mutations, cancer.

BER

Base Excision Repair; fixes small non-bulky lesions; enzymes: glycosylase → AP endonuclease → polymerase → ligase.

NER

Nucleotide Excision Repair; removes bulky UV/chemical lesions; ~30 nt segments.

HR

Homologous recombination; accurate DSB repair using sister chromatid; BRCA1/2, RAD51 involved.

NHEJ

Non-homologous end joining; error-prone DSB repair; can cause mutations; linked to SCID when faulty.

MMR

Mismatch Repair; correcting replication errors; key proteins MSH, MLH.

• BRCA1/BRCA2

BRCA1 regulates repair signaling; BRCA2 recruits RAD51 for HR; mutations linked to HBOC.

Epigenetics

Heritable gene expression changes without DNA sequence change; includes DNA methylation and histone modification.

DNA methylation

Methylation of CpG islands in promoters; generally represses gene expression.

Histone modifications

Post-translational modifications (acetylation, methylation, phosphorylation) modulating chromatin.

Cross-talk: DNA methylation and histones

Methylated DNA recruits HDACs leading to deacetylation and gene silencing.

Epigenetics in cancer – predisposition to mutations

Global hypomethylation promotes genome instability; hypermethylation silences tumor suppressors.

Epigenetic therapy

Therapies targeting epigenetic marks: DNMT inhibitors, HDAC inhibitors, BRD4 inhibitors, IDH inhibitors.

DNA demethylating agents

Agents like 5-azacytidine, decitabine used to reactivate silenced genes.

HDAC inhibitors

Drugs like Vorinostat; re-expression of silenced genes via histone hyperacetylation.

BRD4 inhibitors

Epigenetic therapy targeting bromodomain proteins (e.g., JQ1) to disrupt gene regulation.

IDH1/2 inhibitors

Target mutant IDH enzymes affecting epigenetic state and tumor metabolism.

Inherited cancer syndromes

Genetic predisposition patterns: Sporadic, Familial, Inherited; examples include HBOC (BRCA1/2), HNPCC (MLH1/MSH2), Li-Fraumeni (TP53), MEN2 (RET).

BRCA1/BRCA2 roles

DNA damage response; BRCA1 links damage sensors to repair; BRCA2 recruits RAD51 for HR.

HBOC

Hereditary breast and ovarian cancer syndrome; BRCA1/2 mutations confer risk.

HNPCC (Lynch)

Hereditary nonpolyposis colorectal cancer; MLH1/MSH2 etc.; DNA Mismatch Repair defects.

Paraneoplastic syndromes

Systems-wide effects caused by cancer (hormonal/immune) not due to local tumor.

Tumor markers

Substances produced by tumors or in response to tumors; used mainly for monitoring (e.g., PSA, AFP, CEA, CA 19-9, CA 125).

Molecular diagnostics in cancer

Tools like FISH, PCR, sequencing (NGS); also liquid biopsy for noninvasive tumor DNA.

Oncogenic viruses – HPV

DNA virus; high-risk types (HPV 16/18) cause cervical/anal/oropharyngeal cancers; E6 inhibits p53, E7 inhibits Rb; vaccines Gardasil, Cervarix.

EBV (Epstein-Barr Virus)

DNA virus linked to Burkitt lymphoma and nasopharyngeal carcinoma; establishes latency in B cells.

HHV-8 (KSHV)

Kaposi’s sarcoma herpesvirus; associated with Kaposi sarcoma and Castleman disease; LANA proteins modulate host pathways.

HBV/HCV and cancer

HBV integration and chronic inflammation promote hepatocellular carcinoma (HCC); HCV linked via chronic inflammation.

HTLV-1

Retrovirus causing adult T-cell leukemia/lymphoma; Tax oncoprotein activates oncogenes.

HIV and cancer

Indirect carcinogenesis via immunosuppression; AIDS-defining cancers include Kaposi sarcoma, CLL/NHL.

Antitumor immunity – CD8+ T cells

Cytotoxic T cells killing tumor cells via perforin/granzyme or FasL pathways.

Checkpoint inhibitors

Immunotherapy blocking CTLA-4 or PD-1/PD-L1 to unleash T cells against cancer.

Monoclonal antibodies (mAbs)

Target tumor antigens (e.g., Rituximab targets CD20); can block receptors or recruit immune effectors.

CAR-T cells

Engineered T cells with tumor-specific receptors; highly effective in some B-cell cancers; early-stage.

Oncolytic viruses

Engineered viruses that selectively infect and kill tumor cells (e.g., PVSRIPO).

Non-specific cancer therapies

Surgery, radiotherapy, and conventional chemotherapy that affect both cancer and normal cells.

Surgery (cancer)

Goal: remove tumor mass; may remove micrometastases in select cancers.