Ataxia telangiectasia and Rad3-related inhibition by AZD6738 enhances gemcitabine-induced cytotoxic effects in bladder cancer cells.

The ataxia telangiectasia and rad3-related-checkpoint kinase 1 (ATR-CHK1) pathway is involved in DNA damage responses in many cancer cells. ATR inhibitors have been used in clinical trials in combination with radiation or chemotherapeutics; however, their effects against bladder cancer remain unclear. Here, the efficacy of combining gemcitabine with the novel ATR inhibitor AZD6738 was investigated in vitro in three bladder cancer cell lines (J82, T24, and UM-UC-3 cells).

The Dual Histone Deacetylase-Proteasome Inhibitor RTS-V5 Acts Synergistically With Ritonavir to Induce Endoplasmic Reticulum Stress in Bladder Cancer Cells.

Background/aim: Simultaneous inhibition of histone deacetylase and proteasomes induces endoplasmic reticulum (ER) stress efficiently. RTS-V5 is the first dual histone deacetylase-proteasome inhibitor, and we anticipated that combining it with the cytochrome P450 family 3 subfamily A member 4 inhibitor ritonavir would enhance its activity in bladder cancer cells.

Materials And Methods: Using bladder cancer cells (human T-24, J-82, murine MBT-2), we evaluated the ability and mechanism by which the combination of RTS-V5 and ritonavir induced ER stress and killed cancer cells.

Simvastatin-romidepsin combination kills bladder cancer cells synergistically.

The HMG-CoA reductase inhibitor simvastatin activates AMP-activated protein kinase (AMPK) and thereby induces histone acetylation. We postulated that combining simvastatin with the histone deacetylase (HDAC) inhibitor romidepsin would kill bladder cancer cells by inducing histone acetylation cooperatively. The combination of romidepsin and simvastatin induced robust apoptosis and killed bladder cancer cells synergistically.

Ubiquitin-proteasome System Is a Promising Target for Killing Cisplatin-resistant Bladder Cancer Cells.

Background/aim: Activation of the ubiquitin-proteasome system (UPS) has been shown to be associated with drug resistance in cancer. Using bladder cancer cells, we investigated the association between UPS activation and cisplatin resistance and also the efficacy of UPS-targeting drugs.

Materials And Methods: We established cisplatin-resistant bladder cancer cells (J82-cisR, T24-cisR) and examined the activation status of the UPS and the efficacy of MLN7243, oprozomib, ixazomib, and RTS-V5.

Inhibition of checkpoint kinase 1 potentiates anticancer activity of gemcitabine in bladder cancer cells.

Checkpoint kinases (CHKs) are involved in the DNA damage response in many cancer cells. CHK inhibitors have been used in clinical trials in combination with chemotherapeutics; however, their effect against bladder cancer remains unclear. Here, we investigated the efficacy of combining gemcitabine with MK-8776, a novel CHK1 inhibitor, in four bladder cancer cell lines.

Prostate cancer recurrence mimicking invasive urothelial cancer of the bladder.

A 74-year-old male patient with stage D1 prostate cancer with the initial prostate-specific antigen (PSA) level of 5570 ng/mL had received androgen deprivation therapy and the serum PSA level had decreased to 0.23 ng/mL when he developed macroscopic hematuria. MRI and cystoscopy suggested invasive urothelial cancer of the bladder, and transurethral resection was performed.

Rapid progression of mucinous tubular and spindle cell carcinoma of the kidney without sarcomatoid changes: A case report.

We report a case of unusually aggressive behavior of a mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney with no sarcomatoid changes. A 43-year-old man was referred to our hospital for a mass on his left kidney. Computed tomography revealed a tumor at the upper pole of the kidney and swollen lymph nodes.

Lopinavir-Ritonavir Combination Induces Endoplasmic Reticulum Stress and Kills Urological Cancer Cells.

Background/aim: Induction of endoplasmic reticulum (ER) stress is a novel approach to cancer treatment. This study investigated the ability of the clinically feasible combination of the human immunodeficiency virus protease inhibitors lopinavir and ritonavir to induce ER stress killing urological cancer cells.

Materials And Methods: Renal cancer cells (769-P, 786-O) and bladder cancer cells (UMUC-3, T-24) were used to investigate the ability of the combination to induce ER stress and its mechanism of action.

Fluvastatin potentiates anticancer activity of vorinostat in renal cancer cells.

Drug repositioning is an emerging approach to developing novel cancer treatments. Vorinostat is a histone deacetylase inhibitor approved for cancer treatment, but it could attenuate its anticancer activity by activating the mTOR pathway. The HMG-CoA reductase inhibitor fluvastatin reportedly activates the mTOR inhibitor AMP-activated protein kinase (AMPK), and we thought that it would potentiate vorinostat's anticancer activity in renal cancer cells.

Metformin Augments Panobinostat's Anti-Bladder Cancer Activity by Activating AMP-Activated Protein Kinase.

Panobinostat, a histone deacetylase inhibitor, induces histone acetylation and acts against cancer but attenuates its anticancer activity by activating the mammalian target of rapamycin (mTOR) pathway. AMP-activated protein kinase (AMPK) is a cellular energy sensor that reportedly inhibits the mTOR pathway. The antidiabetic drug metformin is also a potent AMPK activator and we investigated whether it augmented panobinostat's antineoplastic activity in bladder cancer cells (UMUC3, J82, T24 and MBT-2).

Evaluation of Therapeutic Potential of Phenoxodiol, a Novel Isoflavone Analog, in Renal Cancer Cells.

Background/aim: In the present study, the antineoplastic activity and mechanism of action of phenoxodiol, a novel isoflavone analog, was investigated in renal cancer cells.

Materials And Methods: A panel of renal cancer cells (769-P, 786-O, Caki-2) was treated with phenoxodiol in vitro, and the efficacy of treatment was evaluated.

Results: MTS assay results showed that phenoxodiol decreased renal cancer viability in a dose-dependent manner.

Panobinostat and Nelfinavir Inhibit Renal Cancer Growth by Inducing Endoplasmic Reticulum Stress.

Background/aim: There is no curative treatment for patients with advanced renal cancer. We believed that the combination of the histone deacetylase inhibitor panobinostat and the human immunodeficiency virus protease inhibitor nelfinavir would kill renal cancer cells by inducing endoplasmic reticulum (ER) stress.

Materials And Methods: Using renal cancer cells (769-P, 786-O, Caki-2), the ability of this combination to induce ER stress and its mechanism of action were investigated.

Nelfinavir Induces Endoplasmic Reticulum Stress and Sensitizes Renal Cancer Cells to TRAIL.

Background/aim: Induction of endoplasmic reticulum (ER) stress is a novel strategy for cancer treatment. The human immunodeficiency virus protease inhibitor nelfinavir was recently shown to induce ER stress, but its anti-neoplastic activity has never been investigated in renal cancer, as far as we are aware.

Materials And Methods: Using renal cancer cells (769-P, 786-O, Caki-2), the ability of nelfinavir to induce ER stress and sensitize them to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was tested.

Recurrent retroperitoneal soft tissue sarcoma showing drastic reduction after pazopanib administration accompanied by severe liver dysfunction.

Pazopanib is an orally bioavailable tyrosine kinase inhibitor anticancer drug approved worldwide for the treatment of metastatic renal cell carcinoma and advanced soft tissue sarcoma. Here we report the case of a patient whose recurrent retroperitoneal soft tissue sarcoma showed a drastic reduction immediately after pazopanib administration accompanied by severe liver dysfunction. His liver function was restored conservatively by giving him hepatoprotectors and having him stop taking pazopanib.

Delanzomib Interacts with Ritonavir Synergistically to Cause Endoplasmic Reticulum Stress in Renal Cancer Cells.

Background/aim: To investigate the efficacy against renal cancer cells of combining the HIV protease inhibitor ritonavir with the novel proteasome inhibitor delanzomib.

Materials And Methods: Renal cancer cell lines 769-P, 786-O, Caki-2 and Renca were treated with ritonavir and delanzomib in vitro and in vivo, and the efficacy of combination was evaluated.

Results: The combination of ritonavir and delanzomib synergistically inhibited renal cancer growth and suppressed colony formation.

Primary Realignment for Pelvic Fracture Urethral Injury Is Associated With Prolonged Time to Urethroplasty and Increased Stenosis Complexity.

Objective: To compare the clinical courses of patients with pelvic fracture urethral injury (PFUI) according to initial management strategy.

Methods: We reviewed the clinical courses of 63 patients with PFUI who were initially treated elsewhere and underwent delayed anastomotic urethroplasty by a single surgeon between 2008 and 2015. Patients were grouped according to their initial treatment: by suprapubic tube placement alone (49 patients, SPT group) or primary realignment (14 patients, PR group).

Nelfinavir and Ritonavir Kill Bladder Cancer Cells Synergistically by Inducing Endoplasmic Reticulum Stress.

The human immunodeficiency virus (HIV) protease inhibitor nelfinavir acts against malignancies by inducing endoplasmic reticulum (ER) stress. The HIV protease inhibitor ritonavir, on the other hand, not only induces ER stress but also inhibits P-glycoprotein's pump activity and thereby enhances the effects of its substrate drugs. We therefore postulated that ritonavir in combination with nelfinavir would kill bladder cancer cells effectively by inducing ER stress cooperatively and also enhancing nelfinavir's effect.

Ritonavir and ixazomib kill bladder cancer cells by causing ubiquitinated protein accumulation.

There is no curative treatment for advanced bladder cancer. Causing ubiquitinated protein accumulation and endoplasmic reticulum stress is a novel approach to cancer treatment. The HIV protease inhibitor ritonavir has been reported to suppress heat shock protein 90 and increase the amount of unfolded proteins in the cell.

Ritonavir Interacts With Belinostat to Cause Endoplasmic Reticulum Stress and Histone Acetylation in Renal Cancer Cells.

The histone deacetylase (HDAC) inhibitor belinostat increases the amount of unfolded proteins in cells by promoting the acetylation of heat shock protein 90 (HSP90), thereby disrupting its chaperone function. The human immunodeficiency virus protease inhibitor ritonavir, on the other hand, not only increases unfolded proteins by suppressing HSP90 but also acts as a proteasome inhibitor. We thought that belinostat and ritonavir together would induce endoplasmic reticulum (ER) stress and kill renal cancer cells effectively.

Bortezomib and belinostat inhibit renal cancer growth synergistically by causing ubiquitinated protein accumulation and endoplasmic reticulum stress.

There is no curative treatment for advanced renal cancer, and a novel treatment approach is urgently required. Inducing ubiquitinated protein accumulation and endoplasmic reticulum (ER) stress has recently emerged as a new approach in the treatment of malignancies. In the present study, we hypothesized that the histone deacetylase inhibitor belinostat would increase the amount of unfolded proteins in cells by inhibiting heat-shock protein (HSP) 90, and that the proteasome inhibitor bortezomib would inhibit their degradation by inhibiting the proteasome, thus causing ubiquitinated protein accumulation and ER stress synergistically.