Medicine and Health Sciences Commons^™

Targeting Dusps In Glioblastomas–Wielding A Double‐Edged Sword, Sheila Abraham, Swapna Asuthkar, William Lee, Srinivasulu Chigurupat, Andrew Tsung, Kiran Kiran

Sheila Prabhakar Abraham

Several dual-specificity phosphatases (DUSPs) that play key roles in the direct or indirect inactivation of different MAP kinases (MAPKs) have been implicated in human cancers over the past decade. This has led to a growing interest in identifying DUSPs and their specific inhibitors for further testing and validation as therapeutic targets in human cancers. However, the lack of understanding of the complex regulatory mechanisms and cross-talks between MAPK signaling pathways, combined with the fact that DUSPs can act as a double-edged sword in cancer progression, calls for a more careful and thorough investigation. Among the various types of brain cancer, …

3d Thoracoscopic Ultrasound Volume Measurement Validation In An Ex Vivo And In Vivo Porcine Model Of Lung Tumours, V. Hornblower, E. Yu, A. Fenster, J. Battista, R. Malthaner

Richard A. Malthaner

The purpose of this study was to validate the accuracy and reliability of volume measurements obtained using three-dimensional (3D) thoracoscopic ultrasound (US) imaging. Artificial "tumours" were created by injecting a liquid agar mixture into spherical moulds of known volume. Once solidified, the "tumours" were implanted into the lung tissue in both a porcine lung sample ex vivo and a surgical porcine model in vivo. 3D US images were created by mechanically rotating the thoracoscopic ultrasound probe about its long axis while the transducer was maintained in close contact with the tissue. Volume measurements were made by one observer using the …

Is Extended Volume External Beam Radiation Therapy Covering The Anastomotic Site Beneficial In Post-Esophagectomy High Risk Patients?, Edward Yu, Rashid Dar, George Rodrigues, Larry Stitt, Gregory Videtic, Pauline Truong, Anna Tomiak, Robert Ash, Ed Brecevic, Richard Inculet, Richard Malthaner, Mark Vincent, Ian Craig, Walter Kocha, Michael Lefcoe

Richard A. Malthaner

Background and purpose: To assess the impact of extended volume radiation therapy (RT) with anastomotic coverage on local control in high risk post-operative esophageal cancer patients.

Patients and methods: This is a retrospective study of high risk (T(3), T(4), nodes positive, with or without margin involvement) post-operative esophageal cancer patients treated at London Regional Cancer Centre from 1989 to 1999. After esophagectomy, all patients received adjuvant combined modality therapy consisting of four cycles of fluorouracil-based chemotherapy, and loco-regional RT with or without coverage of the anastomotic site. RT dose ranged from 45 to 60 Gy at 1.8-2.0 Gy/fraction with treatment …

Lung Cancer Brachytherapy: Robotics-Assisted Minimally Invasive Approach, Edward Yu, Craig Lewis, Ana Trejos, Rajni Patel, Richard Malthaner

Richard A. Malthaner

New technological concepts have been evolving to manage the relative poor prognosis of lung cancer. Brachytherapy is becoming an option for both unresectable and early resectable lung cancer. Three-dimensional ultrasound (US) of lung tumours and image-guided minimally invasive robotics-assisted brachytherapy are feasible for dosimetry planning and management of lung tumours. The present article reviews the current knowledge of lung brachytherapy and discusses its potential in future management of lung cancer.

Post-Operative Extended Volume External Beam Radiation Therapy In High Risk Esophageal Cancer Patients: A Prospective Experience, E. Yu, P. Tai, J. Younus, R. Malthaner, P. Truong, L. Stitt, G. Rodrigues, R. Ash, R. Dar, B. Yaremko, A. Tomiak, B. Dingle, M. Sanatani, M. Vincent, W. Kocha, D. Fortin, R. Inculet

Richard A. Malthaner

Background and purpose: Extended volume external beam radiation therapy (RT) following esophagectomy is controversial. This prospective study evaluates the feasibility of extended volume RT treatment in high-risk esophagectomy patients with cervical anastomosis receiving post–operative combined chemo-radiation therapy. Patients and methods: From 2001-2006, 15 patients with resected esophageal cancer were prospectively accrued to this pilot study, to evaluate the adverse effects of extended volume RT. Eligibility criteria were pathologically proven esophageal malignancy, T3-4, N0-1, disease amenable to surgical resection and esophagectomy with or without resection margin involvement. Patients with distant metastases (M1) and patients treated with previous RT were excluded. All …

Management And Prognosis In Synchronous Solitary Resected Brain Metastasis From Non–Small-Cell Lung Cancer, Alexander Louie, George Rodrigues, Brian Yaremko, Edward Yu, A. Dar, Brian Dingle, Mark Vincent, Michael Sanatani, Richard Malthaner, Richard Inculet

Richard A. Malthaner

Background: Reports in the medical literature have described cases of extended survival of patients with non-small-cell lung cancer (NSCLC) with solitary metastatic disease who have received aggressive treatment both to the brain metastasis and to the local/regional disease. The objective of this research is to analyze prognostic factors that predict for outcome in this unique patient population.

Patients and methods: A single-institution, retrospective chart review was performed on 35 patients with NSCLC and a synchronous solitary brain metastasis (SSBM) treated with craniotomy and whole-brain radiation therapy. Eight patients (22.9%) had chest surgery, 24 (68.6%) had chemotherapy, and 14 (40%) had …

The Management Of Thymoma: A Systematic Review And Practice Guideline, Conrad Falkson, Andrea Bezjak, Gail Darling, Richard Gregg, Richard Malthaner, Donna Maziak, Edward Yu, Christopher Smith, Sheila Mcnair, Yee Ung, William Evans

Richard A. Malthaner

INTRODUCTION: Thymoma is a rare tumor for which there is little randomized evidence to guide treatment. Because of the lack of high-quality evidence, a formal consensus-based approach was used to develop recommendations on treatment. METHODS: A systematic refview of the literature was performed. Recommendations were formed from available evidence and developed through a two-round modified Delphi consensus approach. RESULTS: The treatment recommendations are summarized as follows: Stage I--complete resection of the entire thymus without neoadjuvant or adjuvant therapy. Stage II--complete resection of the entire thymus with consideration of adjuvant radiation for high-risk tumors. Stage IIIA--surgery either initially or after neoadjuvant …

Neoadjuvant Or Adjuvant Therapy For Resectable Esophageal Cancer: A Systematic Review And Meta-Analysis, Richard Malthaner, Rebecca Wong, R. Rumble, Lisa Zuraw

Richard A. Malthaner

Background: Carcinoma of the esophagus is an aggressive malignancy with an increasing incidence. Its virulence, in terms of symptoms and mortality, justifies a continued search for optimal therapy. The large and growing number of patients affected, the high mortality rates, the worldwide geographic variation in practice, and the large body of good quality research warrants a systematic review with meta-analysis.

Methods: A systematic review and meta-analysis investigating the impact of neoadjuvant or adjuvant therapy on resectable thoracic esophageal cancer to inform evidence-based practice was produced.MEDLINE, CANCERLIT, Cochrane Library, EMBASE, and abstracts from the American Society of Clinical Oncology and the …

Definitive Radiation Therapy Management For Medically Non-Resectable Clinically Localised Non-Small Cell Lung Cancer: Results & Prognostic Factors, Edward Yu, Patricia Tai, Robert Ash, Michael Lee, Larry Stitt, George Rodrigues, Rashid Dar, Mark Vincent, Richard Inculet, Richard Malthaner

Richard A. Malthaner

The aim of this paper is to review the experience of radical radiation therapy and the prognostic factors of patient outcome for clinically localised, medically inoperable non-small cell lung cancer (NSCLC) patients. Clinically staged node-negative NSCLC patients who were not a surgical candidates due to co-morbid diseases but who were eligible for curative treatment, were reviewed in the London Regional Cancer Program (LRCP). This study population was treated between 1st Jan 1985 to 31st Jan 2004. Patients were excluded if they were previously treated with chest radiotherapy. Patients with localised disease, but who refused surgery, were also included in the …

Neoadjuvant Or Adjuvant Therapy For Resectable Esophageal Cancer: A Clinical Practice Guideline, Richard Malthaner, Rebecca Wong, R. Rumble, Lisa Zuraw

Richard A. Malthaner

Background: Carcinoma of the esophagus is an aggressive malignancy with an increasing incidence. Its virulence, in terms of symptoms and mortality, justifies a continued search for optimal therapy. A clinical practice guideline was developed based on a systematic review investigating neoadjuvant or adjuvant therapy on resectable thoracic esophageal cancer. Methods: A systematic review with meta-analysis was developed and clinical recommendations were drafted. External review of the practice guideline report by practitioners in Ontario, Canada was obtained through a mailed survey, and incorporated. Final approval of the practice guideline was obtained from the Practice Guidelines Coordinating Committee. Results: The systematic review …

Cyclosporin Versus Tacrolimus For Liver Transplanted Patients, Elizabeth Haddad, Vivian Mcalister, Elizabeth Renouf, Richard Malthaner, Mette Kjaer, Lise Gluud

Richard A. Malthaner

A systematic review of randomized clinical trials (RCT) was undertaken to evaluate the beneficial and harmful effects of immunosuppression with cyclosporin versus tacrolimus for liver transplanted patients. MEDLINE, EMBASE, Cochrane Central and Hepato-Biliary Group Controlled Trials Registers were searched. Using fixed and random effects model, relative risk (RR), values <1 favoring>tacrolimus, with 95% confidence intervals (CI) were calculated. Of 717 potentially relevant references, 16 RCTs were eligible for inclusion. Mortality and graft loss at 1 year were significantly reduced in tacrolimus-treated recipients (Death: RR 0.85, 95% CI 0.73-0.99; graft loss: RR 0.73, 95% CI 0.61-0.86). Tacrolimus reduced the number of recipients …

Mira V: An Integrated System For Minimally Invasive Robot-Assisted Lung Brachytherapy, A. Trejos, A. Lin, S. Mohan, H. Bassan, C. Edirisinghe, R. Patel, C. Lewis, E. Yu, A. Fenster, R. Malthaner

Richard A. Malthaner

An integrated system for minimally invasive robot-assisted image-guided lung brachytherapy has been developed. The system incorporates an experimental setup for accurate radioactive seed placement with commercially available dosimetry planning software. The end result is a complete system that allows planning and executing a brachytherapy procedure with increased accuracy. The results of the in vitro seed placement evaluation show that seed misplacement has a significant effect on the volume receiving more than 200% of the dose (V200), and the minimum dosage received by 90% of the volume (D90).

3d Thoracoscopic Ultrasound Volume Measurement Validation In An Ex Vivo And In Vivo Porcine Model Of Lung Tumours, V. Hornblower, E. Yu, A. Fenster, J. Battista, R. Malthaner

Richard A. Malthaner

The purpose of this study was to validate the accuracy and reliability of volume measurements obtained using three-dimensional (3D) thoracoscopic ultrasound (US) imaging. Artificial "tumours" were created by injecting a liquid agar mixture into spherical moulds of known volume. Once solidified, the "tumours" were implanted into the lung tissue in both a porcine lung sample ex vivo and a surgical porcine model in vivo. 3D US images were created by mechanically rotating the thoracoscopic ultrasound probe about its long axis while the transducer was maintained in close contact with the tissue. Volume measurements were made by one observer using the …

The 4th Annual Ontario Thoracic Cancer Conference At Niagara-On-The-Lake, Y. Ung, E. Yu, R. Malthaner, R. Burkes, P. Ellis, G. Goss, H. Solow, S. Irvine, S. Laffan

Richard A. Malthaner

The 4th annual Ontario Thoracic Cancer Conference at Niagara-on-the-lake focused on the themes of innova- tions in the management of lung cancer, controversies in the management of esophageal cancer, and molecu- lar targeted therapies in lung cancer. This conference summary highlights the presentations and provides clinicians with a referenced update on these topics.

Is Extended Volume External Beam Radiation Therapy Covering The Anastomotic Site Beneficial In Post-Esophagectomy High Risk Patients?, Edward Yu, Rashid Dar, George Rodrigues, Larry Stitt, Gregory Videtic, Pauline Truong, Anna Tomiak, Robert Ash, Ed Brecevic, Richard Inculet, Richard Malthaner, Mark Vincent, Ian Craig, Walter Kocha, Michael Lefcoe

Richard A. Malthaner

Background and purpose: To assess the impact of extended volume radiation therapy (RT) with anastomotic coverage on local control in high risk post-operative esophageal cancer patients.

Patients and methods: This is a retrospective study of high risk (T(3), T(4), nodes positive, with or without margin involvement) post-operative esophageal cancer patients treated at London Regional Cancer Centre from 1989 to 1999. After esophagectomy, all patients received adjuvant combined modality therapy consisting of four cycles of fluorouracil-based chemotherapy, and loco-regional RT with or without coverage of the anastomotic site. RT dose ranged from 45 to 60 Gy at 1.8-2.0 Gy/fraction with treatment …

Lung Cancer Brachytherapy: Robotics-Assisted Minimally Invasive Approach, Edward Yu, Craig Lewis, Ana Trejos, Rajni Patel, Richard Malthaner

Richard A. Malthaner

New technological concepts have been evolving to manage the relative poor prognosis of lung cancer. Brachytherapy is becoming an option for both unresectable and early resectable lung cancer. Three-dimensional ultrasound (US) of lung tumours and image-guided minimally invasive robotics-assisted brachytherapy are feasible for dosimetry planning and management of lung tumours. The present article reviews the current knowledge of lung brachytherapy and discusses its potential in future management of lung cancer.

Post-Operative Extended Volume External Beam Radiation Therapy In High Risk Esophageal Cancer Patients: A Prospective Experience, E. Yu, P. Tai, J. Younus, R. Malthaner, P. Truong, L. Stitt, G. Rodrigues, R. Ash, R. Dar, B. Yaremko, A. Tomiak, B. Dingle, M. Sanatani, M. Vincent, W. Kocha, D. Fortin, R. Inculet

Richard A. Malthaner

Background and purpose: Extended volume external beam radiation therapy (RT) following esophagectomy is controversial. This prospective study evaluates the feasibility of extended volume RT treatment in high-risk esophagectomy patients with cervical anastomosis receiving post–operative combined chemo-radiation therapy. Patients and methods: From 2001-2006, 15 patients with resected esophageal cancer were prospectively accrued to this pilot study, to evaluate the adverse effects of extended volume RT. Eligibility criteria were pathologically proven esophageal malignancy, T3-4, N0-1, disease amenable to surgical resection and esophagectomy with or without resection margin involvement. Patients with distant metastases (M1) and patients treated with previous RT were excluded. All …

Subsets More Likely To Benefit From Surgery Or Prophylactic Cranial Irradiation After Chemoradiation For Localized Non-Small-Cell Lung Cancer, Bruce Keith, Mark Vincent, Larry Stitt, Anna Tomiak, Richard Malthaner, Edward Yu, Pauline Truong, Richard Inculet, Michael Lefcoe, A. Dar, Walter Kocha, Ian Craig

Richard A. Malthaner

After chemoradiation for localized non-small-cell lung cancer, surgery and prophylactic cranial irradiation (PCI) have been used as additional therapies. Less than a third of patients develop brain recurrences, or have local recurrence as their sole initial site of recurrence; these are groups that would benefit from PCI or surgery, respectively. Pretreatment identification of patients more likely to benefit from surgery or PCI would be useful. A retrospective analysis of 80 patients was performed to determine prognostic factors for such patterns of failure. Twenty-nine patients were subsequently selected for surgery in a nonrandomized manner. Seventeen patients had isolated local initial recurrence …

Management And Prognosis In Synchronous Solitary Resected Brain Metastasis From Non–Small-Cell Lung Cancer, Alexander Louie, George Rodrigues, Brian Yaremko, Edward Yu, A. Dar, Brian Dingle, Mark Vincent, Michael Sanatani, Richard Malthaner, Richard Inculet

Richard A. Malthaner

Background: Reports in the medical literature have described cases of extended survival of patients with non-small-cell lung cancer (NSCLC) with solitary metastatic disease who have received aggressive treatment both to the brain metastasis and to the local/regional disease. The objective of this research is to analyze prognostic factors that predict for outcome in this unique patient population.

Patients and methods: A single-institution, retrospective chart review was performed on 35 patients with NSCLC and a synchronous solitary brain metastasis (SSBM) treated with craniotomy and whole-brain radiation therapy. Eight patients (22.9%) had chest surgery, 24 (68.6%) had chemotherapy, and 14 (40%) had …

The Management Of Thymoma: A Systematic Review And Practice Guideline, Conrad Falkson, Andrea Bezjak, Gail Darling, Richard Gregg, Richard Malthaner, Donna Maziak, Edward Yu, Christopher Smith, Sheila Mcnair, Yee Ung, William Evans

Richard A. Malthaner

INTRODUCTION: Thymoma is a rare tumor for which there is little randomized evidence to guide treatment. Because of the lack of high-quality evidence, a formal consensus-based approach was used to develop recommendations on treatment. METHODS: A systematic refview of the literature was performed. Recommendations were formed from available evidence and developed through a two-round modified Delphi consensus approach. RESULTS: The treatment recommendations are summarized as follows: Stage I--complete resection of the entire thymus without neoadjuvant or adjuvant therapy. Stage II--complete resection of the entire thymus with consideration of adjuvant radiation for high-risk tumors. Stage IIIA--surgery either initially or after neoadjuvant …

Neoadjuvant Or Adjuvant Therapy For Resectable Esophageal Cancer: A Systematic Review And Meta-Analysis, Richard Malthaner, Rebecca Wong, R. Rumble, Lisa Zuraw

Richard A. Malthaner

Background: Carcinoma of the esophagus is an aggressive malignancy with an increasing incidence. Its virulence, in terms of symptoms and mortality, justifies a continued search for optimal therapy. The large and growing number of patients affected, the high mortality rates, the worldwide geographic variation in practice, and the large body of good quality research warrants a systematic review with meta-analysis.

Methods: A systematic review and meta-analysis investigating the impact of neoadjuvant or adjuvant therapy on resectable thoracic esophageal cancer to inform evidence-based practice was produced.MEDLINE, CANCERLIT, Cochrane Library, EMBASE, and abstracts from the American Society of Clinical Oncology and the …

Definitive Radiation Therapy Management For Medically Non-Resectable Clinically Localised Non-Small Cell Lung Cancer: Results & Prognostic Factors, Edward Yu, Patricia Tai, Robert Ash, Michael Lee, Larry Stitt, George Rodrigues, Rashid Dar, Mark Vincent, Richard Inculet, Richard Malthaner

Richard A. Malthaner

The aim of this paper is to review the experience of radical radiation therapy and the prognostic factors of patient outcome for clinically localised, medically inoperable non-small cell lung cancer (NSCLC) patients. Clinically staged node-negative NSCLC patients who were not a surgical candidates due to co-morbid diseases but who were eligible for curative treatment, were reviewed in the London Regional Cancer Program (LRCP). This study population was treated between 1st Jan 1985 to 31st Jan 2004. Patients were excluded if they were previously treated with chest radiotherapy. Patients with localised disease, but who refused surgery, were also included in the …

Neoadjuvant Or Adjuvant Therapy For Resectable Esophageal Cancer: A Clinical Practice Guideline, Richard Malthaner, Rebecca Wong, R. Rumble, Lisa Zuraw

Richard A. Malthaner

Background: Carcinoma of the esophagus is an aggressive malignancy with an increasing incidence. Its virulence, in terms of symptoms and mortality, justifies a continued search for optimal therapy. A clinical practice guideline was developed based on a systematic review investigating neoadjuvant or adjuvant therapy on resectable thoracic esophageal cancer.

Methods: A systematic review with meta-analysis was developed and clinical recommendations were drafted. External review of the practice guideline report by practitioners in Ontario, Canada was obtained through a mailed survey, and incorporated. Final approval of the practice guideline was obtained from the Practice Guidelines Coordinating Committee.

Results: The systematic review …

What Factors Predict Outcome At Relapse After Previous Esophagectomy And Adjuvant Therapy In High-Risk Esophageal Cancer?, Edward Yu, Patricia Tai, Richard Malthaner, Larry Stitt, George Rodrigues, Rashid Dar, Brian Yaremko, Jawaid Younus, Michael Sanatani, Mark Vincent, Brian Dingle, Dalilah Fortin, Richard Inculet

Richard A. Malthaner

Management of patients who have disease relapse after completion of surgery and adjuvant chemo-radiation (CRT) is controversial. Some oncologists would advocate intensive therapeutic intervention due to promising experience on treatment for recurrence disease while others would recommend palliative support due to the concerns for poor patient outcome post disease recurrence. In Addition, it is not clear if patient outcome is improved post adjuvant CRT when patients at risk have resection margin involvement and if time interval to recurrence can affect patient survival post relapse. The present study was conducted to determine what factors will affect patient outcome at relapse after …

Cyclosporin Versus Tacrolimus For Liver Transplanted Patients, Elizabeth Haddad, Vivian Mcalister, Elizabeth Renouf, Richard Malthaner, Mette Kjaer, Lise Gluud

Richard A. Malthaner

A systematic review of randomized clinical trials (RCT) was undertaken to evaluate the beneficial and harmful effects of immunosuppression with cyclosporin versus tacrolimus for liver transplanted patients. MEDLINE, EMBASE, Cochrane Central and Hepato-Biliary Group Controlled Trials Registers were searched. Using fixed and random effects model, relative risk (RR), values <1 favoring>tacrolimus, with 95% confidence intervals (CI) were calculated. Of 717 potentially relevant references, 16 RCTs were eligible for inclusion. Mortality and graft loss at 1 year were significantly reduced in tacrolimus-treated recipients (Death: RR 0.85, 95% CI 0.73-0.99; graft loss: RR 0.73, 95% CI 0.61-0.86). Tacrolimus reduced the number of recipients …

Mira V: An Integrated System For Minimally Invasive Robot-Assisted Lung Brachytherapy, A. Trejos, A. Lin, S. Mohan, H. Bassan, C. Edirisinghe, R. Patel, C. Lewis, E. Yu, A. Fenster, R. Malthaner

Richard A. Malthaner

An integrated system for minimally invasive robot-assisted image-guided lung brachytherapy has been developed. The system incorporates an experimental setup for accurate radioactive seed placement with commercially available dosimetry planning software. The end result is a complete system that allows planning and executing a brachytherapy procedure with increased accuracy. The results of the in vitro seed placement evaluation show that seed misplacement has a significant effect on the volume receiving more than 200% of the dose (V200), and the minimum dosage received by 90% of the volume (D90).

The 4th Annual Ontario Thoracic Cancer Conference At Niagara-On-The-Lake, Y. Ung, E. Yu, R. Malthaner, R. Burkes, P. Ellis, G. Goss, H. Solow, S. Irvine, S. Laffan

Richard A. Malthaner

The 4th annual Ontario Thoracic Cancer Conference at Niagara-on-the-lake focused on the themes of innova- tions in the management of lung cancer, controversies in the management of esophageal cancer, and molecu- lar targeted therapies in lung cancer. This conference summary highlights the presentations and provides clinicians with a referenced update on these topics.

Subsets More Likely To Benefit From Surgery Or Prophylactic Cranial Irradiation After Chemoradiation For Localized Non-Small-Cell Lung Cancer, Bruce Keith, Mark Vincent, Larry Stitt, Anna Tomiak, Richard Malthaner, Edward Yu, Pauline Truong, Richard Inculet, Michael Lefcoe, A. Dar, Walter Kocha, Ian Craig

Richard A. Malthaner

After chemoradiation for localized non-small-cell lung cancer, surgery and prophylactic cranial irradiation (PCI) have been used as additional therapies. Less than a third of patients develop brain recurrences, or have local recurrence as their sole initial site of recurrence; these are groups that would benefit from PCI or surgery, respectively. Pretreatment identification of patients more likely to benefit from surgery or PCI would be useful. A retrospective analysis of 80 patients was performed to determine prognostic factors for such patterns of failure. Twenty-nine patients were subsequently selected for surgery in a nonrandomized manner. Seventeen patients had isolated local initial recurrence …

Alcohol And Hcv: Implications For Liver Cancer, Gyongyi Szabo, Banishree Saha, Terence Bukong

Gyongyi Szabo

Liver cancers are one of the deadliest known malignancies which are increasingly becoming a major public health problem in both developed and developing countries. Overwhelming evidence suggests a strong role of infection with hepatitis B and C virus (HBV and HCV), alcohol abuse, as well as metabolic diseases such as obesity and diabetes either individually or synergistically to cause or exacerbate the development of liver cancers. Although numerous etiologic mechanisms for liver cancer development have been advanced and well characterized, the lack of definite curative treatments means that gaps in knowledge still exist in identifying key molecular mechanisms and pathways …

Crosstalk Between Desmoglein 2 And Patched 1 Accelerates Chemical-Induced Skin Tumorigenesis., Donna M Brennan-Crispi, Claudia Hossain, Joya Sahu, Mary Brady, Natalia A Riobo, M G Mahoney

Claudia Hossain

Aberrant activation of Hedgehog (Hh) signaling is causative of BCCs and has been associated with a fraction of SCCs. Desmoglein 2 (Dsg2) is an adhesion protein that is upregulated in many cancers and overexpression of Dsg2 in the epidermis renders mice more susceptible to squamous-derived neoplasia. Here we examined a potential crosstalk between Dsg2 and Hh signaling in skin tumorigenesis. Our findings show that Dsg2 modulates Gli1 expression, in vitro and in vivo. Ectopic expression of Dsg2 on Ptc1+/lacZ background enhanced epidermal proliferation and interfollicular activation of the Hh pathway. Furthermore, in response to DMBA/TPA, the Dsg2/Ptc1+/lacZ mice developed squamous …