cisplatin powder (Randa / IA CALL)

Initial Evaluation of Dihydroartemisinin (DHA), Metformin and Taro Extract in Combination with Cisplatin for Enhanced Cytotoxicity in Triple-Negative Breast Cancer (TNBC) Cell Lines.

Godwin Ada Morgan AM, Ward Na'Turie N, Krauss Christopher C, Banerjee Hirendranath H et al.

This study evaluated the antiproliferative effects of cisplatin, dihydroartemisinin, metformin and taro extract on MDA-MB-231 triple-negative breast cancer (TNBC) cell lines. Cisplatin at half maximal inhibitory concentration, IC50 (20 μM) induced ~45% cell death (p < 0.001 vs control), while metformin (MET), dihydroartemisinin (DHA), and taro extract (TE) alone showed minimal cell death. Combination treatments (Cis + MET, Cis + DHA, and Cis + TE) significantly increased cytotoxicity to ~60% cell death on average (p < 0.01 vs cisplatin alone), with Cis + TE producing the greatest effect (~90%). The triple metabolic combination without cisplatin caused less than10% cell death (p < 0.001 vs cisplatin-containing groups), probably supporting a cisplatin-dependent cell death.

TIP60 promotes chemoresistance by limiting intracellular platinum accumulation and enhancing removal of cisplatin-DNA adducts.

Hira Akshay A, Craig Michael P MP, McLaughlin Caroline C, Zhang Jin J et al.

Cisplatin resistance is a major barrier to effective treatment of squamous cell carcinoma (SCC) including cutaneous SCC and Head and neck SCC, where resistance develops in more than half of advanced cases. Our previous work demonstrated that genetic knockdown or pharmacological inhibition of TIP60 (KAT5), a histone acetyl transferase, sensitizes cisplatin-resistant SCC cells, induces cell cycle arrest and promotes cell death, suggesting a key role for TIP60 in mediating resistance. Here, we use cisplatin-sensitive and resistant SCC cell lines, together with siRNA-mediated gene silencing, stable overexpression, pharmacological inhibition, immunodot-blot assays, and ICP-MS to demonstrate that TIP60 promotes resistance through two complementary pathways: (1) upregulation of the efflux transporter ABCC1, which reduces intracellular cisplatin accumulation, and (2) increased expression of XPC, a key component of the nucleotide excision repair pathway, involved in recognition and removal of cisplatin-DNA adducts. Elevated TIP60 levels correlate with reduced cisplatin-DNA adduct levels, enhanced removal of cisplatin-DNA adducts and increased cell survival in resistant lines. TIP60 depletion reduces ABCC1 expression and increases cisplatin-DNA adduct levels, effects similarly observed with the ABCC1 inhibitor, MK-571. In parallel, TIP60 knockdown impairs removal of cisplatin-DNA adducts and reduces expression of multiple DNA damage response (DDR) genes, including XPC. Combined inhibition of TIP60 with spironolactone (targeting XPB/NER) or with MK-571further reduces cell survival and increases cell death in resistant cells. These findings establish TIP60 as a regulator of cisplatin resistance that integrates drug efflux and DNA repair pathways, highlighting TIP60 inhibition as a promising therapeutic strategy to overcome platinum resistance in SCC.

Effect of reusing cobalt-chromium alloy powders in direct metal laser sintering on powder characteristics and metal-ceramic bond strength.

Berk Taha Yasin TY, Çelik Öge Selin S, Uçar Yurdanur Y, Ekren Orhun O

The purpose of this in vitro study was to evaluate the effect of reusing Co-Cr alloy powders without addition of new powder on powder characteristics, ion release, and metal-ceramic bond strength. Co-Cr alloy powders consisting of virgin powder (G1) and powders reused through the 4th (G4), 7th (G7), 10th (G10), and 13th (G13) manufacturing cycles of a DMLS system were analyzed by scanning electron microscopy (SEM), laser particle size distribution (LPSD), and X-ray diffraction (XRD). Bar-shaped Co-Cr specimens (0.5 × 3 × 25 mm) were fabricated with DMLS from the corresponding powder groups (n = 15), veneered with porcelain according to ISO 9693-1, and tested for metal-ceramic bond strength using 3-point bending. Ion release was measured with inductively coupled plasma mass spectrometry (ICP-MS). Bond strength data was analyzed with 1-way analysis of variance and Dunnett T3 tests (α = .05), and Weibull analysis was performed for reliability assessment. No significant differences were found in metal-ceramic bond strength among the groups (P > .05). Mean bond strength values ranged from 56.8 ± 8.2 MPa (G7) to 78.2 ± 39.5 MPa (G13). SEM analyses revealed progressive powder deformation with increasing reuse cycles, whereas LPSD analysis demonstrated only slight changes in particle size distribution (d50: 23.4-23.7 μm). XRD analysis demonstrated similar cubic-phase characteristics among all groups. ICP-MS analysis demonstrated increased Co, Mo, and W ion release with increasing powder reuse, whereas Cr remained undetectable in all groups. Repeated reuse of Co-Cr alloy powders without virgin powder adding did not adversely affect metal-ceramic bond strength but resulted in progressive morphological deformation and increased ion release with increasing reuse cycles.

[Expression of Concern] In vitro and in vivo targeting of bladder carcinoma with metformin in combination with cisplatin.

Wang Dong D, Wu Xiaohou X