• Cavernous nerve injury by radiotherapy potentiates erectile dysfunction in rats

      Connors, Caroline; Mahmood, Javed (2017)
      Approximately 50% of prostate cancer patients receiving radiotherapy develop erectile dysfunction within 3-5 years. The precise role of radiation-induced neurogenic injury post-radiotherapy has not been fully established. The CNs are post-ganglionic parasympathetic nerves that assist in the penile erection, located beside the prostate. Male rats were exposed to RT, and erectile function, CN injury, and penile tissue damage were evaluated. Physiological, electrophysiological, and TEM analysis elucidated the extent of damage to CN. RT also significantly increased the mRNA and protein expression of neural damage markers in the MPG. A significant upregulation of both RhoA/ROCK1 mRNA and ROCK1 protein expression were observed in radiated MPG. This result will introduce a rationale for utilizing novel strategies to prevent CN damage post-RT, and the RhoA/ROCK signaling pathway could be a feasible future target pathway to mitigate RiED in prostate cancer patients.

      Singh, Prerna; Mahmood, Javed (2019)
      Chordomas are a rare slow-growing cancer and their standard of care is surgery with Radiotherapy (RT). Chordoma is highly radioresistant and requires high dose of RT that lead to toxicity in the surrounding tissues. We investigated whether proton beam radiation therapy (PBRT) response can be further enhanced in combination with hyperthermia (HT) as a radiosensitizer. We also explored cell survival at the end of the Spread-out Bragg Peak (E-SOBP) compared to middle of the SOBP (M-SOBP) of PBRT with and without HT. Chordoma cell lines were treated with HT followed by PBRT at both E-SOBP and M-SOBP. Clonogenic assay was performed in triplicates for a dose response survival. HT with PBRT significantly killed (p<0.05) more cells at M-SOBP and E-SOBP compared to PBRT without HT. Our results provide in vitro evidence on effects of HT as a novel additive treatment to increase PBRT effectiveness in Chordoma cell lines.
    • Tripartite treatment by radiation, hyperthermia and anti-OX40 immunotherapy potentiates tumor growth delay and tumor microenvironment immunomodulation in pancreatic cancer

      Alexander, Allen Abey; Mahmood, Javed; 0000-0002-1825-1161 (2017)
      Pancreatic cancer is the fourth most deadly cancer in the United States. Despite development in conventional treatment strategies the 5 year survival rate is only 7.7%. In this study we demonstrated that the tripartite treatment by combination of fractionated radiation therapy, hyperthermia and anti-OX40 immunotherapy (tripartite) led to significant impact on pancreatic cancer in mice. The treatment of mice with the tripartite treatment demonstrated significant tumor growth inhibition (p<0.0001) with no observable toxicity due to this treatment. Flow cytometric analysis of the tumor showed a shift in tumor microenvironment from immune suppressive to immune stimulatory with significantly higher CD4+ and CD8a+ (p<0.05) T lymphocytes. A significantly higher population of helper T cells and cytotoxic T cells was observed in the usually immune-deficient pancreatic cancer tumor microenvironment coupled with a decrease in the immunosuppressive microenvironment in the tumors of animals receiving the tripartite treatment is potentially the cause of the superior anti-tumor effect observed in animals receiving the tripartite treatment.