Journal: Cell Death & Disease

Article Title: Dual inhibition of mTOR and HSP90 enhances cisplatin efficacy and overcomes resistance in ovarian cancer

doi: 10.1038/s41419-026-08533-3

Figure Lengend Snippet: A CI (combination index) values (mean ± SD from at least three separate experiments performed in quadruplicates) computed at 50% (CI50), 75% (CI75) and 90% (CI90) of cell kill by CalcuSyn software after 96 h for TOV-112D and TOV-112D Pt-res cl.7 cells. The treatments are indicated in the figure. The combinations were considered synergistic when CIs were below 0.9, additive when CIs were between 0.9 and 1.1 or antagonism when Cis were more than 1.1. B DRI (doses reduction index) values (mean ± SD) for CDDP from at least three separate experiments performed in quadruplicate) that represent the order of magnitude (fold) of dose reduction obtained for IC50 (DRI50) in combination setting compared with each drug alone in TOV-112D and TOV-112D Pt-res cl.7 cells. C Synergistic inhibition of colony formationin TOV-112D and TOV-112D Pt-res cl.7 treated with CDDP, ganetespib, temsirolimus or their combination (simultaneous exposure) at the IC 10 96h doses for parental cells. Representative data of at least three independent experiments performed in triplicates. Statistically significant results calculated with one-way ANOVA test are reported (a indicates control group, b indicates CDDP-treated cells, and c indicates ganetespib-treated cells, d indicates temsirolimus-treated cells, e indicates cddp plus ganetespib-treated cells * P < 0.05, ** P < 0.01, *** P < 0.001 and **** P < 0.0001, ns, not statistically significant). D Synergistic inhibition of microtissues formation by CDDP, ganetespib, temsirolimus alone and in combination. Cancer cells (red ones-marked by cell tracker) and mice fibroblast cells NIH/3T3 were plated in each well and after 24 h treated withIC 50 96h doses of parental cells. Representative images from Opera Phenix confocal microscopy. The graphics represent the number of viable cells in 3D cell culture based on quantitation of the ATP content. Results were obtained by a single experiment performed in triplicate ( ± SD). Statistically significant results calculated with one-way ANOVA test are reported (a indicates control group, b indicates CDDP-treated cells, and c indicates ganetespib-treated cells, d indicates temsirolimus-treated cells, e indicates CDDP plus ganetespib-treated cells * P < 0.05, ** P < 0.01, *** P < 0.001 and **** P < 0.0001, ns not statistically significant).

Article Snippet: Temsirolimus (Torisel®) was provided by Pfizer.

Techniques: Software, Inhibition, Control, Confocal Microscopy, Cell Culture, Quantitation Assay

Journal: Cell Death & Disease

Article Title: Dual inhibition of mTOR and HSP90 enhances cisplatin efficacy and overcomes resistance in ovarian cancer

doi: 10.1038/s41419-026-08533-3

Figure Lengend Snippet: A Apoptosis and necrosis evaluated by flow cytometry after Annexin V-FITC and propidium iodide staining in TOV-112D and TOV-112D Pt-res cl. 7, untreated or treated for 24 h or 48 h, with temsirolimus, CDDP plus ganetespib and CDDP plus ganetespib and temsirolimus at IC 50 96h doses of parental cells. B Western blot analysis of cleaved PARP1 in TOV-112D and TOV-112D Pt-res cl. 7 cells untreated or treated with CDDP, ganetespib, temsirolimus and their combinationat IC 50 96h doses of parental cells at the time indicated above. β-actin expression serves as loading control. Western blot quantification was performed by ImageJ software. C Western blot analysis of γH2AX in TOV-112D and TOV-112D Pt-res cl. 7 cells untreated or treated with CDDP, ganetespib, temsirolimus and their combination at IC 50 96h doses of parental cells at the time indicated above. β-actin expression serves as loading control. Western blot quantification was performed by ImageJ software.

Article Snippet: Temsirolimus (Torisel®) was provided by Pfizer.

Techniques: Flow Cytometry, Staining, Western Blot, Expressing, Control, Software

Journal: Cell Death & Disease

Article Title: Dual inhibition of mTOR and HSP90 enhances cisplatin efficacy and overcomes resistance in ovarian cancer

doi: 10.1038/s41419-026-08533-3

Figure Lengend Snippet: Western blot analysis, performed after 48 h of treatment, of the main proteins (indicated in the figure) involved in mTOR mediated signaling pathway ( A ), HSF1 dependent transactivation ( B ) and chaperone complex ( C ) in TOV-112D Pt-res cl. 7 cells untreated or treated with CDDP, ganetespib, temsirolimus, and their combination at IC 50 96h doses of parental cells. β-actin expression serves as loading control. Western blot quantification was performed by ImageJ software.

Article Snippet: Temsirolimus (Torisel®) was provided by Pfizer.

Techniques: Western Blot, Expressing, Control, Software

Journal: Cell Death & Disease

Article Title: Dual inhibition of mTOR and HSP90 enhances cisplatin efficacy and overcomes resistance in ovarian cancer

doi: 10.1038/s41419-026-08533-3

Figure Lengend Snippet: A Schematic of the in vivo xenograft experiment, including timeline and agent concentration. TOV-112D Pt-res cl.7 cells (6 × 10 6 ) were s.c. injected into NSG mice as described in Materials and Methods. When tumors were established, mice were treated once a week for two weeks with vehicles (CTR) or temsirolimus (20 mg kg −1 i.p.) or CDDP (2.5 mg kg −1 i.p.) and ganetespib (GANE; 30 mg kg −1 i.p.) or triple CDDP/ganetespib/temsirolimus combination. B Relative tumor volume (TV) measured at prespecified time points (Means ± SEM). C Mice body weight as surrogate indicator of toxicity for in vivo experiment reported in A. Body weight was measured three times/week. D TGD, indicating the mean rate of tumor growth in the treatment groups relative to control untreated mice (see Materials and Methods). E Percent change in tumor volume average from first day of treatment (day 0) to day 28 for each treatment group compared to vehicles group. F Kaplan–Meier curves comparing the survival of single and combination groups of treatment. Statistically significant results calculated with one-way ANOVA test comparing ganetespib plus CDDP and ganetespib/temsirolimus plus CDDP are reported (* P < 0.05 and **** P < 0.0001).

Article Snippet: Temsirolimus (Torisel®) was provided by Pfizer.

Techniques: In Vivo, Concentration Assay, Injection, Control

Journal: bioRxiv

Article Title: Fibroblast-derived Collagen VI shapes the structure and function of the tumor-immune microenvironment in clear cell renal cell carcinoma

doi: 10.64898/2026.03.19.712351

Figure Lengend Snippet: ( A ) Survival analysis for high or low expression of COL6A1 and COL6A2 in the CheckMate 025 study cohort of Nivolumab (anti-PD-1) or everolimus (mTOR inhibitor) treated patients . Graphs show Kaplan-Meier plots and Log-rank (Mantel-Cox) tests. (B-D) Analysis of COL6 deposition in CDMs treated with cabozantinib (Cabo.), sunitinib (Suni.), temsirolimus (Temsi.), or DMSO (Ctrl.) treated TK173 cells. (B) Dot plot depicting relative median fluorescence intensities (MFI) of COL6 in CDMs of respectively treated cells in the screening experiment (N=10 regions of interest, one-way ANOVA with Tukey’s multiple comparison test). (C) Dot plot depicting mean relative MFI of COL6 in CDMs of respectively treated TK173 cells (dots indicate mean of N=4 independent experiments, unpaired t test). (D) IF images stained for FN (green) and COL6 (violet) of synthesized CDMs of TK173 cells treated with the indicated drugs. (E) Schematic description of RNA sequencing analysis of cabozantinib or DMSO control-treated TK173 fibroblasts and acute organotypic slice cultures (OTSCs) of ccRCCs (Created in BioRender. Schell, C. (2026) https://BioRender.com/x5sqb3y ). (F&G) Volcano plot of differential gene expression analysis of matrisome genes in cabozantinib-treated TK173 cells and ccRCC OTSCs. The inserts depict a volcano plot of all genes. Red dots indicate significantly regulated genes with adjusted p<0.01 and log 2 fold change (FC) > |1|). (H) Heatmap analysis of significantly regulated matrisome genes in cabozantinib-treated TK173 cells and ccRCC OTSCs (genes with adjusted p<0.0001 and fold change > |2| are depicted for TK173 cells or with adjusted p<0.01 and fold change > |1.5| for OTSCs). (I) Heatmap analysis of log 2 expression fold changes (FC) of immunomodulatory genes in TK173 cells and ccRCC OTSCs (N/A – not announced). (J&K) IF validation of COL6 regulation in cabozantinib-treated ccRCC OTSCs. Images show IF staining for Nuclei by Hoechst (blue), CK (yellow) and COL6A1 (violet) of OTSCs treated with the indicated drugs. Quantification of COL6A1-positive areas in OTSCs of 10 ccRCC patients (dots indicate individual patients analyzed, ratio paired t test). (L) Schematic summary illustrating the findings of the study, highlighting COL6 expression in tumor stroma as well as the remodeling of the ECM architecture in dependence of COL6 abundance and the subsequent implications for cancer and immune cells (Created in BioRender. Schell, C. (2026) https://BioRender.com/x5sqb3y ).

Article Snippet: Inhibitors used and respective working concentrations are 5 μM cabozantinib (S1119, Selleck Chemicals, Houston, TX, USA), 10 μM sunitinib (S1042, Selleck Chemicals, Houston, TX, USA) and 10 μM temsirolimus (S1044, Selleck Chemicals, Houston, TX, USA), medium was changed every second day.

Techniques: Expressing, Fluorescence, Comparison, Staining, Synthesized, RNA Sequencing, Control, Gene Expression, Biomarker Discovery