癌薬物療法は癌細胞の生存戦略をいかに攻略するかの歴史である。本綜説では，殺細胞性抗癌剤から分子標的薬，そして免疫チェックポイント阻害薬（ICI）へと至る変遷を辿り，特に肝細胞癌（HCC）における複合療法の理論的基盤と，実臨床における効率的な逐次治療の重要性について考察した。従来の抗癌剤は増殖の速い細胞を無差別に攻撃するため，肝予備能の低いHCC患者では治療継続が困難であった。21世紀に入り，ドライバー変異を標的とした分子標的薬が次々と開発され，HCCでは血管新生阻害を主軸としたマルチキナーゼ阻害薬の有効性が示された。さらに癌細胞に対する免疫を回避するための機構である，PD-1/PD-L1を標的としたICIが登場した。HCCでは抗PD-1抗体単剤の効果が限定的で，抗CTLA-4抗体あるいは抗VEGF抗体の併用により高い治療効果を示した。各治療レジメンの治療効果は無作為化比較試験により証明される一方で，臨床現場では，それら治療をどのような順番で行うかは課題となっている。HCC治療は，単一の薬剤選択から薬剤特性を理解した上での戦略的な組み合わせと順序立ての時代へと移行した。耐性機序を考慮した柔軟な逐次治療の構築こそが，患者予後を最大化するための鍵である。

　Background：Microcirculatory dysfunction following percutaneous coronary intervention（ PCI） has received limited attention in recent years. This prospective, single-center study aimed to quantify the incidence and determinants using the index of microvascular resistance（ IMR） after stent implantation in the left anterior descending artery（ LAD）.
　Methods：Thirty adults with stable coronary artery disease underwent elective LAD PCI using contemporary drug-eluting stents between November 2022 and March 2024. IMR, coronary flow reserve（ CFR）, and fractional flow reserve（ FFR） were measured using a pressure-sensing guidewire before and after PCI. High-sensitivity troponin T（ hsTnT） levels were measured before and 16‒24 hours after PCI. The patients were divided into groups based on whether the IMR increased or decreased after PCI.
　Results：The mean patient age was 73±11 years, and 76.6% were male. Overall, CFR improved from 2.3 ±1.2 to 3.1±1.4, and FFR from 0.73±0.08 to 0.86±0.05. Mean IMR decreased modestly from 24±13 to 21±14, yet 40% of patients experienced an IMR increase. The baseline characteristics, lesion severity, stent size, and plaque morphology were similar between the groups. However, hsTnT levels were significantly higher in the IMR increase group（ 143.5 [55.6-265.0] vs. 41.6 [27.5-72.8] ng/L, p=0.009）.
　Conclusions：IMR increased after LAD PCI in 40 . 0% of patients. Patients with increased IMR showed higher hs-TnT levels 16‒24 h after PCI, suggesting an association between post-PCI changes in microvascular resistance and minor myocardial injury. Further validation in larger multicenter studies is warranted.

　Background：The role of hypothiocyanous acid （HOSCN）, generated by the enzymatic activities of myeloperoxidase（ MPO） and lactoperoxidase（ LPO）, in airway inflammation remains poorly understood. Our prior research has demonstrated that HOSCN induces interleukin-6 （IL-6） expression in airway epithelial cell lines （NCI-H292 cells）. However, the underlying mechanisms remain elusive. The aim of this study was to elucidate the signaling molecules and pathways essential for the induction of IL-6 gene expression, thereby providing more robust evidence that HOSCN may contribute to airway inflammation.
　Materials and Methods：Glucose oxidase was added to the LPO- and thiocyanate-containing cell culture medium to serve as a source of hydrogen peroxide for HOSCN production. Under these experimental conditions, we achieved cell stimulation and analyzed key signaling molecules involved in the induction of IL-6 gene expression using western blotting, quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay.
　Results and Discussion：We identified p38 and extracellular signal-regulated kinase （ERK） as critical signaling molecules in HOSCN-induced IL-6 gene expression in NCI-H292 cells. Moreover, the findings indicate that the protein kinase C-mitogen-activated protein kinase/ERK-ERK （PKC-MEKERK） pathway is essential for this induction, strongly implying that it activates transcription factors such as p65 and c-Fos. HOSCN may activate PKC by modifying thiol groups.
　Conclusions：HOSCN, the primary enzymatic reaction product of MPO and LPO, induced IL-6 gene expression in airway epithelial cell lines through the PKC-MEK-ERK signaling pathway. The present results may elucidate the mechanisms underlying the pathogenesis of inflammatory diseases closely associated with MPO and LPO. Furthermore, our findings may contribute to the development of therapeutic interventions for such conditions.