Howard H Pai

Publications (4)6.73 Total impact

• Article: Castration induces autoantibody and T cell responses that correlate with inferior outcomes in an androgen-dependent murine tumor model.

  Sara Hahn, Nancy J Nesslinger, Robert J Drapala, Mary Bowden, Paul S Rennie, Howard H Pai, Charles Ludgate, Brad H Nelson
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  ABSTRACT: We recently reported that hormone therapy induces antigen-specific autoantibody responses in prostate cancer patients. However, the contribution of autoantibody responses to clinical outcomes is unknown. We used an animal model to test the hypothesis that hormone therapy-induced immune responses may be associated with delayed tumor recurrence. Male DD/S mice bearing established tumors from the androgen-dependent Shionogi carcinoma line were castrated to induce tumor regression. Tumor-specific autoantibody responses were measured by immunoblot, and the underlying antigen was identified by serological screening of a cDNA expression library. T cell responses were assessed by immunohistochemistry and IFN-gamma ELISPOT. Following castration, 97% of mice underwent complete tumor regression. Of these, 72% experienced tumor recurrence 18-79 days postcastration, whereas the remaining 28% remained tumor-free for the duration of the experiment. In 55% of mice, castration induced autoantibody responses to an antigen identified as poly(A) binding protein nuclear 1 (PABPN1). Castration also induced PABPN1-specific T cell responses, which were highly correlated to autoantibody responses, and this was accompanied by dense infiltration of tumors by CD3+ T cells 1-2 weeks after castration. Unexpectedly, mice that developed autoantibody and T cell responses to PABPN1 showed a higher rate and shorter latency of tumor recurrence. In mice with recurrent tumors, T cell responses to PABPN1 were still detectable; however, T cell infiltrates were restricted to the peripheral stroma of tumors. In conclusion, castration-induced immune responses are associated with inferior outcomes in the Shionogi carcinoma model, raising concerns about the influence of treatment-induced immune responses on clinical outcomes in humans.
  International Journal of Cancer 07/2009; 125(12):2871-8. · 5.44 Impact Factor
• Chapter: Effects of Standard Treatments on the Immune Response to Prostate Cancer

  Nancy J. Nesslinger, Howard H. Pai, Charles M. Ludgate, Brad H. Nelson
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  ABSTRACT: Prostate cancer is the most frequently diagnosed cancer in North American men and, despite improvements in early detection due to prostate-specific antigen (PSA) screening, it remains the second leading cause of cancer-related death among men. Standard treatment for localized disease includes radical prostatectomy, external beam radiation therapy (EBRT), and brachytherapy, which are often combined with hormone therapy in high risk patients. These treatments are successful in controlling organconfined disease; however if tumors recur, the disease is typically systemic and hormone therapy remains the only treatment option. While hormone therapy is initially efficacious, patients eventually progress to androgen-independent disease, which is incurable. Immune-based treatments such as cancer vaccines are emerging as a treatment option for those patients with hormone-refractory disease, however the results to date from clinical trials, while promising, do not yet warrant the adoption of immunotherapy as standard of care. Further progress will require a deeper understanding of the interactions between the immune system and prostate cancer. Although we have some understanding of the natural host response to prostate cancer at the time of diagnosis, far less is known regarding the state of tumor immunity at the completion of standard treatments and beyond, despite the fact that this is the immunological context in which immunebased treatments must operate if the goal is to prevent or delay recurrence. One can imagine that standard treatments, by causing tumor cell death in an inflammatory context, must have an impact on the host immune response. Do standard treatments enhance or inhibit host immunity to prostate cancer? Does host immunity have a significant influence on clinical outcomes? If standard treatments fail, does this in part reflect a failure of the immune system? And finally, how can we best enhance the immune response to tip the balance in favor of tumor stabilization or rejection? We begin this discussion by reviewing the concepts, technical issues, and evidence concerning the effect of standard treatments on tumor-specific immunity in prostate cancer.
  12/2007: pages 531-555;
• Article: What is the optimal duration of androgen deprivation therapy in prostate cancer patients presenting with prostate-specific antigen levels > 20 ng/ml?

  Eric Berthelet, Tom Pickles, Pauline T Truong, Mitchell Liu, Howard H Pai, Winkle B Kwan, Jan T W Lim
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  ABSTRACT: To evaluate the optimal duration of androgen deprivation therapy (ADT) in patients with prostate cancer treated with external beam radiotherapy (EBRT), who present with PSA levels > 20 ng/mL. A total of 307 patients presenting with a PSA > 20 ng/ml were treated with EBRT and ADT. The cohort was divided into four groups according to the duration of ADT: Group 1 received < 6 months (n = 71), group 2 received 6-12 months (n = 80), group 3 received 12-24 months (n = 72), and group 4 received > 24 months (n = 84) of ADT. The endpoints analyzed were biochemical control (bNED), overall survival (OS) and cause-specific survival (CSS). Statistical analysis was conducted using Kaplan-Meier estimates and Cox regression models. Compared to patients who received < 6 months of ADT, patients treated with 12-24 months or > 24 months of ADT experienced significantly improved bNED (p = 0.01 and p < 0.0001, respectively). Cause-specific survival with ADT durations 12-24 and > 24 months were significantly higher compared to < 6 months (p < 0.007 and 0.024, respectively). Overall survival with ADT durations > 24 months was also significantly higher compared to < 6 months (p = 0.0025). The present analysis supports the hypothesis that longer durations of ADT improves bNED, CSS and OS in patients presenting with a PSA > 20 ng/ml.
  The Canadian Journal of Urology 08/2007; 14(4):3621-7. · 0.64 Impact Factor
• Article: Web-based electronic health information systems for prostate cancer patients.

  Howard H Pai, Francis Lau
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  ABSTRACT: Providing men with prostate cancer (MPC) timely access to their health records and information (HRI) can enhance their ability to understand their condition and engage in shared medical decision making with their health care provider (HCP). The Internet is a potential means of enhancing such interactions. Two surveys were conducted at a PC support group in Victoria, BC to identify the health information needs of MPC and the ability to access their HRI. Another objective was to identify the potential role of web-enabled HRI systems at meeting these needs. Sixty-one participants (41 men and 18 spouses/significant others (SS)) completed the first convenience survey and 16 participants then took part in a focus group meeting using a second questionnaire. The majority of men (median age 70 years) were knowledgeable with the computer and Internet. The majority of men (75%) desired the ability to access their HRI through means other than by meeting with their HCP, with the Internet ranking as one of the most desired methods. There was broad interest in accessing various parts of their health record and during different phases of their care. Most men were willing to try a personalized patient web-enabled HRI system. Over 70% of SS desired the ability to access their men's HRI. The surveys indicate that the Internet is a desirable means of accessing electronic HRI and support the potential role of web-enabled HRI systems for PC patients.
  The Canadian Journal of Urology 07/2005; 12(3):2700-9. · 0.64 Impact Factor