Chapter 23. Medicine
Recommended Article: 【Biology】 Biology Index
1. Disease
2. Diagnosis
3. Treatment
1. Disease
⑴ Category 1. Cancer
⑵ Category 2. Organ-based Functional Disorders
① 2-1. Respiratory System Diseases
② 2-2. Metabolic Diseases
○ Intestinal diseases
○ Liver diseases
○ Diabetes mellitus
③ 2-3. Skin (dermatologic) diseases
○ Liver fibrosis
○ Lung fibrosis
○ Idiopathic pulmonary fibrosis
○ Scleroderma
④ 2-4. Neurodegenerative Diseases
○ Neurological disorders
⑶ Category 3. Immune System Diseases
① 3-1. Infectious diseases: viral diseases, etc.
② 3-2. Inflammatory diseases
③ 3-3. Autoimmune diseases
④ 3-4. Immune-evasion diseases: AIDS, etc.
⑷ Category 4. Aging: there is a recent perspective that regards aging as a disease.
2. Diagnosis
⑴ Diagnosis – Histopathology
① Tumor Tissue: Nuclei are larger compared to normal cells.
Figure 1. Tumor Tissue
② Tumor and Gland Tissue
Figure 2. Tumor and Gland Tissue
③ Normal Epithelial Cells
Figure 3. Normal Epithelial Cells
④ Intestinal Metaplasia
Figure 4. Intestinal Metaplasia
⑤ Lymphoid Follicles
Figure 5. Lymphoid Follicles
⑥ Muscularis Mucosa
Figure 6. Muscularis Mucosa
⑦ Peritumoral Muscularis
Figure 7. Peritumoral Muscularis
⑧ Lamina Propria
Figure 8. Lamina Propria
⑨ Blood-Containing Tissue
Figure 9. Blood-Containing Tissue
⑩ Connective Tissue
Figure 10. Connective Tissue
⑪ Immune Clusters: Higher cell density and larger nuclei compared to other cells.
⑵ Diagnosis – Blood Pressure
① Normal: Systolic BP 90-119 mmHg, Diastolic BP 60-79 mmHg
② Prehypertension: Systolic BP 120-139 mmHg, Diastolic BP 80-89 mmHg
③ Hypertension Stage 1: Systolic BP 140-159 mmHg, Diastolic BP 90-99 mmHg
④ Hypertension Stage 2: Systolic BP > 160 mmHg, Diastolic BP > 100 mmHg
⑶ Diagnosis – Pulmonary Function Test (PFT)
① Forced Vital Capacity (FVC): Maximum amount of air that can be exhaled.
② Forced Expiratory Volume in 1 Second (FEV1): Amount of air exhaled in 1 second.
③ % = FEV1 / FVC × 100
④ Normal: % = 70
⑤ Obstructive: % ↓
⑥ Restrictive: % ↑
⑷ Diagnosis – Glomerular Filtration Rate (GFR)
Table 1. GFR Scale
⑸ Evaluation – RECIST (Response Evaluation Criteria in Solid Tumors)
① Evaluation criteria for solid cancers
○ Serves as both a biomarker and a clinical outcome.
② Complete Response (CR)
○ All target and non-target lesions have disappeared.
○ And the short axis of every lymph node is < 10 mm.
③ Partial Response (PR)
○ Target lesions have decreased by ≥ 30%.
○ And non-target lesions are at least not progressing.
④ Stable Disease (SD)
○ Cases that do not clearly meet PR or PD.
⑤ Progressive Disease (PD)
○ Target lesions have increased by ≥ 20%, or non-target lesions have progressed.
○ Or new lesions have appeared.
⑹ Evaluation – TNM Staging: assessment of the tumor stage
① T (Tumor): subdivided by size and relationship to adjacent tissues.
② N (Node metastasis): metastasis to the lymphatic system.
③ M (Distant metastasis): metastasis via the bloodstream.
⑺ Evaluation – HAS-BLED Score: assesses bleeding risk
① Scoring table
| Clinical features | Score (point) |
|---|---|
| H Hypertension: SBP > 160 mmHg | 1 |
| A Abnormal liver function | 1 |
| A Abnormal renal function | 1 |
| S Stroke history | 1 |
| B Prior major bleeding / predisposition to bleeding | 1 |
| L Labile INR on Warfarin | 1 |
| E Elderly; age > 65 years | 1 |
| D Drugs predisposing bleeding: antiplatelet / NSAIDs | 1 |
| D High alcohol consumption | 1 |
| Maximum score | 9 |
Table 2. Table of HAS-BLED score evaluation
② Evaluation: 0 is low risk, 1-2 is moderate risk, 3+ is high risk.
⑻ Assessment – Breslow thickness
① Classification system for primary melanoma
② Classification criteria: < 1 mm, 1–2 mm, 2.1–4 mm, > 4 mm
⑼ Prediction - HER-2 Grading System
① Predicts effectiveness of HER-2 targeted treatment by assessing HER-2 expression qualitatively through IHC.
| HER-2 grade | Explanation | Interpretation |
|---|---|---|
| 0 | No reactivity or membranous reactivity in < 10% of tumor cells. | Negative |
| 1 | Faint / barely perceptible membranous reactivity is detected in > 10% of tumor cells. | Negative |
| The cells are immunoreactive only in part of the membrane. | ||
| 2 | Weak to moderate complete membranous reactivity is seen in > 10% of tumor cells. | Borderline reactivity |
| 3 | Strong complete reactivity is seen in > 10% of tumor cells. | Positive |
Table 3. HER-2 grading system
⑽ Prognosis – Gleason’s Pattern Scale
3. Treatment
⑴ Method 1. Surgery
① Tumor Resection
○ The criteria are established by Hermanek et al. 15 years ago.
○ R0 resection: microscopically margin-negative resection
○ R1 resection: removal of all macroscopic disease. May contain micropic margin.
○ R2 resection: Gross residual disease containing primary tumor, regional node, macroscopic margin.
⑵ Method 2. Chemotherapy
⑶ Method 3: Radiotherapy
① Principles (the “5 Rs”)
○ Repair: Repair of sublethal damage allows normal cells to recover.
○ Redistribution: Cancer cells in S phase are relatively resistant. By delivering radiation in multiple fractions, more cells are irradiated in non-S phases, improving tumor cell kill.
○ Reoxygenation: As some cancer cells die, oxygen influx increases, which raises radiation sensitivity.
○ Repopulation: With repeated irradiation, the proportion of normal cells to cancer cells changes.
○ Radiosensitivity: Sensitivity to radiation therapy varies by cell type and tissue.
② Type 1: External Beam Radiotherapy
○ IMRT: The current standard.
○ 3D-CRT: Conforms to the tumor shape but cannot modulate beam intensity.
③ Type 2: Brachytherapy
④ Adverse effects
○ Crossfire irradiation: A nuclide bound to the target cell also causes adjacent cells to incur radiation damage.
○ Bystander effect: When the target cell undergoes apoptosis, neighboring cells are affected by its apoptotic signaling.
⑷ Method 4. Immunotherapy
① Overview: Immunotherapy is effective in only 12.5% of cancer patients.
② Types 1. Cancer vaccine
③ 1-1. Prophylactic cancer vaccines: HPV vaccine, hepatitis B vaccine, etc. Only two are FDA-approved.
○ Voretigene neparvovec (Luxturna): 2017
○ AAV2-based: expresses the RPE65 gene.
○ RPE65 gene: encodes a 65-kDa protein in the human retinal pigment epithelium.
○ Onasemnogene abeparvovec (Zolgensma): 2019
○ AAV9-based.
○ Encodes the survival motor neuron (SMN) protein.
○ If homozygous for an SMN1 gene mutation, spinal muscular atrophy develops within two years after birth.
④ 1-2. Sipuleucel-T
○ An example of a therapeutic cancer vaccine
○ 1st. Extract antigen-presenting cells (APCs) from the patient.
○ 2nd. Expose the APCs to the antigen in vitro.
○ 3rd. Reinfuse the “trained” APCs back into the patient.
○ Used for the treatment of prostate cancer.
○ Advantage: enables one-to-one personalized therapy.
⑤ Type 2. CAR (chimeric antigen receptor) T-cell therapy
○ 1st. Isolate T cells from the patient’s blood.
○ 2nd. Introduce an inactive virus to the T cells to make them express an engineered receptor.
○ 3rd. Expand the cells until there are millions of cells.
○ 4th. Infuse them into the patient → cancer treatment
○ Works well for hematologic cancers but not as well for solid tumors.
○ Reason: unlike blood cancers, the tumor microenvironment of solid tumors diminishes CAR-T activity.
○ Currently, there are five FDA-approved CAR-T therapies.
○ Tisagenlecleucel (Kymriah): 2017
○ Axicabtagene ciloleucel (Yescarta): 2017
○ Brexucabtagene autoleucel (Tecartus): 2020
○ Lisocabtagene maraleucel (Breyanzi): 2021
○ Iidecabtagene vicleucel (Abecma): 2021
⑥ Type 3. Cytokine: IL-2, interferon-alpha, etc.
⑦ Type 4. ICI (Immune Checkpoint Inhibitor), also known as ICB (Immune Checkpoint Blockade)
○ Principle
Figure. 11. The principle of ICI
○ PD-1: Expressed in T cells
○ CTLA-4: Expressed in T cells
○ PD-L1: Expressed in macrophages or tumor cells
○ VISTA: Expressed in T cells, TAM (tumor-associated macrophages), dendritic cells, and other immune cells
○ Siglec: The Siglec family in immune cells binds to sialylated glycans on cancer cells, acting as an immune checkpoint
○ MYC: Overexpression of MYC is involved in immune suppression
○ Type 1. PD-1 inhibitor
○ nivolumab (Opdivo)
○ pembrolizumab (Keytruda, approved for TNBC patients)
○ cemiplimab (Libtayo)
○ Type 2. PD-L1 inhibitor
○ atezolizumab (Tecentriq, approved for TNBC patients)
○ avelumab (Bavencio)
○ durvalumab (Imfinzi)
○ atezolizumab
○ Type 3. CTLA-4 inhibitor
○ ipilimumab (the first ICI discovered)
○ Advantages
○ Universally applicable regardless of cancer type
○ Received FDA approval for mutation burden: This universality was a first
○ Disadvantages
○ Immune-related adverse effect: Can cause autoimmune diseases
○ Shows a response rate of approximately 20-40%: Attempts targeted therapy using mutation burden and other biomarkers
○ Ineffective for cold tumors like glioblastoma
○ Expensive
○ PD-L1 sensitivity may continuously change during treatment
○ Treatment
○ Better treated with anti-PD1/L1 therapy than with anti-CTLA-4 therapy → Anti-PD1, anti-PDL1 drugs are dominating
○ FDA approval condition: Prescribed for solid tumors when specific conditions such as MSI-H (microsatellite instability), MMR (mismatch-repair gene) are met.
⑸ Method 5. Photodynamic Therapy
① PS (Photosensitizer)
② Type I Reaction: PS → 1PS* (singlet state) → 3PS* (triplet state)
○ 1PS* and 3PS* generate radicals, causing tissue damage
③ Type II Reaction: 3PS* + O2 → PS + 1O2*
○ 1O2* (singlet oxygen) causes tissue damage
④ Disadvantages
○ Efficiency decreases in hypoxic conditions: due to the type II reaction. Prolonged exposure to low-intensity light can be one workaround.
○ Photosensitizers (PS) are hydrophobic and can be highly toxic: makes parenteral (injection) administration difficult.
○ If PS present in the skin is exposed to sunlight, cutaneous tissues can be damaged.
○ Limited tissue penetration of visible light (and other wavelengths) is problematic.
Input: 2022-05-05 11:32
Last Revised: 2023-06-04 17:50