Lois Chandler - Academia.edu (original) (raw)
Papers by Lois Chandler
Advances in Wound Care
To compare outcomes of diabetic foot ulcers (DFUs) treated with a collagen Wound Conforming Matri... more To compare outcomes of diabetic foot ulcers (DFUs) treated with a collagen Wound Conforming Matrix (WCM) or standard of care (SOC). Approach: WCM, a highly purified homogenate of 2.6% fibrillar bovine dermal collagen that conforms to the wound surface, was evaluated in comparison to daily saline-moistened gauze dressing changes (SOC) as part of a retrospective subset analysis of a randomized controlled trial in DFU. Following a 2-week run-in period during which patients received SOC, patients whose wounds did not reduce in area by >30% during run-in were randomly assigned to receive WCM (one or two applications) or SOC. Results: Statistically significant acceleration of early healing rates was observed following a single application of WCM with weekly outer dressing changes compared with daily saline-moistened gauze dressing changes (SOC). Over a 4-week period, 50% of patients receiving a single application of WCM achieved ‡75% reduction in wound area compared with 13% for SOC. WCM appeared to be safe and well tolerated, with no adverse events related to treatment and no evidence of an immunologic reaction to bovine collagen. Innovation: WCM is unique in its intimate contact with the wound bed and its ability to progress a wound toward healing with a single application. Conclusion: WCM is a treatment modality to accelerate DFU healing rates, with the potential to reduce the likelihood of infection and other complications, and cost of care.
Human gene therapy, Feb 16, 2018
Gendicine (Recombinant Human p53 Adenovirus, AdRSV-p53), developed by Shenzhen SiBiono GeneTech C... more Gendicine (Recombinant Human p53 Adenovirus, AdRSV-p53), developed by Shenzhen SiBiono GeneTech Company, was approved by CFDA in 2003. It has been used in clinical oncology for 12 years since it entered the market in 2004. As the first-in-class product for cancer gene therapy, Gendicine met its expectation and demonstrated with ample clinical data that it is safe and effective for treating cancer. SiBiono manufactured 41 batches in compliant with CFDA QC/QA requirements. Total 169,571 vials (1.0x1012 vector particles per vial) were used in more than 50,000 patients, among them about 5,000 were international form over 50 nations outside China. Comparing with the first-line standard therapies, intratumor injection of Gendicine combined with chemotherapy and radiotherapy resulted in response rate significantly higher than chemo or radiotherapy alone. The approved indication for Gendicine is Head & Neck Cancer, including NPC. However, Gendicine has been successfully applied for various ...
Cancer Research, Jun 1, 1986
Restriction endonucleaseanalysis was usedto determine the methyla tion status of collagen, c-Ha-r... more Restriction endonucleaseanalysis was usedto determine the methyla tion status of collagen, c-Ha-rn,, and thymidine kinase genes in human fibroblasts and tumor cell lines. When digested with the methylation sensitiveenzymesHpaII or H1UZI, the DNA of each cell line generated a unique banding pattern for each gene examined. No geaeralized trend of gene hypomethylation or decreases in overall cytosine methylation were observed in tumor cell lines when compared to fibroblasts. Collagen biosynthetic profiles were also determined, and no correlations could be made between patterns of type I and type III collagen gene methylation and expression. Our fIndingSsupport those of a previousreport in which methylation and expressionof the chick a2(I) collagengenewere exam ined,and this represents the first such analysis ofthe pro-aI(Ill) collagen gene. MspI restriction fragment length polymorphisms were detected within c-Ha-ras, pro-a2(I) collagen, pro-aI(III) collagen, and thymidhie ki5nasegenes. The ras gene polymorphismscan be attributed to variation in the number of tandem repeats within a MspI fragment at the 3' end of the gene. The other gene polymorphisms may be due to base pair mutations at methylated cytosine residues within CCGG sequences.
Wounds a Compendium of Clinical Research and Practice, 2004
Cancer Research, Jun 1, 1986
We have developeda methodfor the extraction ofDNA fromformalin fixed, paraffin-embedded pathology... more We have developeda methodfor the extraction ofDNA fromformalin fixed, paraffin-embedded pathology specimens. High-molecular-weight DNA was recovered from well-fixed nonautolyzed samples of viable tissue. DNA recovered from samples exposed to picric acid or mercuric chloride containing fixatives was not intact. Increasing the formalin fixation time decreased the amount of intact DNA available. When these limitations were taken into consideration, the procedure allowed for the removal ofdegraded and chemically modified DNA from the preparation, and the final productwas suitable for quantitativeand qualitativeanalysis by Southern or dot blotting techniques. Digestion with methylation sensitive restriction endonucleases showed that DNA methylation pat term were not altered after formalin fixation. INTRODUCFION The field of molecular biology has expanded rapidly over the last few years, and a large amount of new information has accumulated on the organization of the human genome. The genome is not as static as previously thought, and gene rear rangement (1), amplification (2), deletion (3), mutation (4), and altered DNA methylation patterns (5, 6) are examples of deter minants now thought to be important for the regulation of gene expression. Similar modifications are also thought to take place in neoplastic processes and may have prognostic significance.
Wounds a Compendium of Clinical Research and Practice, 2004
Advances in Skin & Wound Care, 2015
Endocrine Abstracts, 2015
Ostomy/wound management, 2013
Clinicians treating pressure ulcers in the elderly in long-term care often face psychosocial, fin... more Clinicians treating pressure ulcers in the elderly in long-term care often face psychosocial, financial, and patient quality-of-life challenges; as such, they seek to identify products that meet wound healing goals as expeditiously as possible. The purpose of this case series was to evaluate outcomes of serial sharp debridement and the application of a formulated collagen gel in patients with chronic, nonhealing pressure ulcers. Three patients (two women ages 82 and 74 years of age and one man 82 years old, all incontinent of bladder and bowel with numerous comorbidities) had wounds >18 months' duration on the buttocks or coccyx that failed to improve despite the use of a wide variety of treatments, including negative pressure wound therapy. All wounds were debrided at the start of treatment and weekly thereafter if necessary, followed by application of the collagen gel. The gel was covered with a sterile bordered gauze and, if needed, a semipermeable dressing. Dressings were...
Molecular and cellular biology, 1994
Although loss of cell surface fibronectin (FN) is a hallmark of many oncogenically transformed ce... more Although loss of cell surface fibronectin (FN) is a hallmark of many oncogenically transformed cells, the mechanisms responsible for this phenomenon remain poorly understood. The present study utilized the nontumorigenic human osteosarcoma cell line TE-85 to investigate the effects of induced Ha-ras oncogene expression on FN biosynthesis. TE-85 cells were stably transfected with metallothionein-Ha-ras fusion genes, and the effects of metal-induced ras expression on FN biosynthesis were determined. Induction of the ras oncogene, but not proto-oncogene, was accompanied by a decrease in total FN mRNA and protein levels. Transfection experiments indicated that these oncogene effects were not due to reduced FN promoter activity, suggesting that a posttranscriptional mechanism was involved. The most common mechanism of posttranscriptional regulation affects cytoplasmic mRNA stability. However, in this study the down-regulation of FN was identified as a nuclear event. A component of the ra...
Wound Repair and Regeneration, 2011
We assessed the safety and efficacy of Formulated Collagen Gel (FCG) alone and with Ad5PDGF-B (GA... more We assessed the safety and efficacy of Formulated Collagen Gel (FCG) alone and with Ad5PDGF-B (GAM501) compared with Standard of Care (SOC) in patients with 1.5-10.0 cm 2 chronic diabetic neuropathic foot ulcers that healed < 30% during Run-in. Wound size was assessed by planimetry of acetate tracings and photographs in 124 patients. Comparison of data sets revealed that acetate tracings frequently overestimated areas at some sites. For per-protocol analysis, 113 patients qualified using acetate tracings but only 82 qualified using photographs. Prior animal studies suggested that collagen alone would have little effect on healing and would serve as a negative control. Surprisingly trends for increased incidence of complete closure were observed for both GAM501 (41%) and FCG (45%) vs. Standard of Care (31%). By photographic data, Standard of Care had no significant effect on change in wound radius (mm/week) from during Run-in to Week 1 (À0.06 AE 0.32 to 0.78 AE 1.53, p5ns) but both FCG (À0.08 AE 0.61 to 1.97 AE 1.77, p < 0.002) and GAM501 (À0.02 AE 0.58 to 1.46 AE 1.37, p < 0.002) significantly increased healing rates that gradually declined over subsequent weeks. Both GAM501 and FCG appeared to be safe and well tolerated, and alternate dosing schedules hold promise to improve overall complete wound closure in adequately powered trials.
Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research, 1991
The basal level of fibronectin (FN) biosynthesis is greatly reduced in N-ras-transformed human fi... more The basal level of fibronectin (FN) biosynthesis is greatly reduced in N-ras-transformed human fibrosarcoma HT1080 cells when compared with normal fibroblasts. The rate of FN biosynthesis can be significantly increased in HT1080 cells by the synthetic glucocorticoid dexamethasone, which has been shown to act by selectively stabilizing the FN message (D.C. Dean, R.F. Newby, and S. Bourgeois, J. Cell Biol., 106: 2159-2170, 1988). The present study demonstrates that the basal levels of FN biosynthesis and accumulated FN mRNA are also reduced in HT1080 cells when compared with nontumorigenic revertants of HT1080 cells in which the mutated N-ras allele is underrepresented. In contrast, the FN promoter is more active in HT1080 cells than in the revertant cells. These results indicate that the down-regulation of FN in HT1080 cells is linked to expression of the N-ras oncogene and that the effect is posttranscriptional. Therefore, the N-ras oncogene and glucocorticoids have opposite posttra...
The Molecular Biology of Cell Determination and Cell Differentiation, 1988
Although numerous possible functions of eukaryotic DNA methylation have been proposed (Ehrlich an... more Although numerous possible functions of eukaryotic DNA methylation have been proposed (Ehrlich and Wang, 1981), current evidence suggests an association between hypomethylation of specific gene regions and transcriptional activity (Doerfler, 1983; Riggs and Jones, 1983). Considerable excitement has been generated by the finding that potential methylation sites are often clustered at the 5&amp;#39; regions of genes (Bird et al., 1985). Furthermore, these clusters appear to be protected from methylation when associated with actively expressed genes. These findings have generated a new line of thinking among researchers, namely that genes may be regulated by domains of methylation sites (Jones, 1986). Although the evidence supporting a role for methylation in eukaryotic gene regulation is convincing, it is by no means unequivocal (Bird, 1984). To date, however, determination of the methylation status of specific cytosine residues in DNA has been limited by the experimental tools at hand. Therefore, development of a method that allows for evaluation of the methylation status of all CpG sites within, and in the vicinity of, genes may be necessary to elucidate the exact relationship between DNA methylation and gene expression. The emerging consensus is that DNA methylation is one component of a hierarchy of control mechanisms that regulate eukaryotic gene expression and cellular differentiation. Furthermore, the realization that methylation plays an important role in regulating gene expression during normal cellular differentiation suggests that aberrations in this potential controlling mechanism may be implicated in the abnormal gene expression seen in cancer. Indeed, a large body of experimental evidence demonstrates altered levels and patterns of methylation in tumor cells (Riggs and Jones, 1983; Jones, 1986). The regulatory function of 5-mCyt is most likely exerted via DNA-protein interactions. Two key questions remain unanswered: How does 5-mCyt affect these interactions? More importantly, what are the proteins that modulate DNA methylation during differentiation?
Wound Repair and Regeneration, 2009
The results from a Phase 1/2 study of a replication-defective adenovirus encoding human platelet-... more The results from a Phase 1/2 study of a replication-defective adenovirus encoding human platelet-derived growth factor (PDGF)-B formulated in a bovine collagen (Ad-5PDGF-B; 2.6% collagen; GAM501) gel for nonhealing neuropathic diabetic foot ulcers is reported. The primary objectives of the study were to evaluate the safety, maximum-tolerated dose, and preliminary biological activity of GAM501. Fifteen patients enrolled into the study with chronic, nonhealing ulcers received either a single administration of GAM501 at one of three dose levels, or up to four administrations of GAM501 at 1-week intervals. All patients received standard of care treatment including debridement and were required to wear an off-loading shoe. GAM501 was found to be safe and well tolerated with no evidence of systemic or local toxicity at all doses so no maximum-tolerated dose was reached. Serum antibody titers to platelet-derived growth factor-B homodimer and collagen were negative and adenoviral DNA was not detected in the blood. In the 12 patients that completed the study, ulcer closure was observed by Month 3 in 10 patients, seven of whom received a single application of GAM501. In conclusion, GAM501 did not appear to have any toxicity at doses that showed biological activity. GAM501 holds promise as a potentially effective treatment for nonhealing diabetic foot ulcers. Ad5-PDGF-B Adenovirus serotype 5 encoding PDGF-B DPN Diabetic peripheral neuropathy GAM Gene activated matrix GAM501 Ad5-PDGF-B in 2.6% collagen PCR Polymerase chain reaction PDGF-BB Platelet-derived growth factor-B homodimer SOC Standard of care vp Viral particle number
Advances in Wound Care
To compare outcomes of diabetic foot ulcers (DFUs) treated with a collagen Wound Conforming Matri... more To compare outcomes of diabetic foot ulcers (DFUs) treated with a collagen Wound Conforming Matrix (WCM) or standard of care (SOC). Approach: WCM, a highly purified homogenate of 2.6% fibrillar bovine dermal collagen that conforms to the wound surface, was evaluated in comparison to daily saline-moistened gauze dressing changes (SOC) as part of a retrospective subset analysis of a randomized controlled trial in DFU. Following a 2-week run-in period during which patients received SOC, patients whose wounds did not reduce in area by >30% during run-in were randomly assigned to receive WCM (one or two applications) or SOC. Results: Statistically significant acceleration of early healing rates was observed following a single application of WCM with weekly outer dressing changes compared with daily saline-moistened gauze dressing changes (SOC). Over a 4-week period, 50% of patients receiving a single application of WCM achieved ‡75% reduction in wound area compared with 13% for SOC. WCM appeared to be safe and well tolerated, with no adverse events related to treatment and no evidence of an immunologic reaction to bovine collagen. Innovation: WCM is unique in its intimate contact with the wound bed and its ability to progress a wound toward healing with a single application. Conclusion: WCM is a treatment modality to accelerate DFU healing rates, with the potential to reduce the likelihood of infection and other complications, and cost of care.
Human gene therapy, Feb 16, 2018
Gendicine (Recombinant Human p53 Adenovirus, AdRSV-p53), developed by Shenzhen SiBiono GeneTech C... more Gendicine (Recombinant Human p53 Adenovirus, AdRSV-p53), developed by Shenzhen SiBiono GeneTech Company, was approved by CFDA in 2003. It has been used in clinical oncology for 12 years since it entered the market in 2004. As the first-in-class product for cancer gene therapy, Gendicine met its expectation and demonstrated with ample clinical data that it is safe and effective for treating cancer. SiBiono manufactured 41 batches in compliant with CFDA QC/QA requirements. Total 169,571 vials (1.0x1012 vector particles per vial) were used in more than 50,000 patients, among them about 5,000 were international form over 50 nations outside China. Comparing with the first-line standard therapies, intratumor injection of Gendicine combined with chemotherapy and radiotherapy resulted in response rate significantly higher than chemo or radiotherapy alone. The approved indication for Gendicine is Head & Neck Cancer, including NPC. However, Gendicine has been successfully applied for various ...
Cancer Research, Jun 1, 1986
Restriction endonucleaseanalysis was usedto determine the methyla tion status of collagen, c-Ha-r... more Restriction endonucleaseanalysis was usedto determine the methyla tion status of collagen, c-Ha-rn,, and thymidine kinase genes in human fibroblasts and tumor cell lines. When digested with the methylation sensitiveenzymesHpaII or H1UZI, the DNA of each cell line generated a unique banding pattern for each gene examined. No geaeralized trend of gene hypomethylation or decreases in overall cytosine methylation were observed in tumor cell lines when compared to fibroblasts. Collagen biosynthetic profiles were also determined, and no correlations could be made between patterns of type I and type III collagen gene methylation and expression. Our fIndingSsupport those of a previousreport in which methylation and expressionof the chick a2(I) collagengenewere exam ined,and this represents the first such analysis ofthe pro-aI(Ill) collagen gene. MspI restriction fragment length polymorphisms were detected within c-Ha-ras, pro-a2(I) collagen, pro-aI(III) collagen, and thymidhie ki5nasegenes. The ras gene polymorphismscan be attributed to variation in the number of tandem repeats within a MspI fragment at the 3' end of the gene. The other gene polymorphisms may be due to base pair mutations at methylated cytosine residues within CCGG sequences.
Wounds a Compendium of Clinical Research and Practice, 2004
Cancer Research, Jun 1, 1986
We have developeda methodfor the extraction ofDNA fromformalin fixed, paraffin-embedded pathology... more We have developeda methodfor the extraction ofDNA fromformalin fixed, paraffin-embedded pathology specimens. High-molecular-weight DNA was recovered from well-fixed nonautolyzed samples of viable tissue. DNA recovered from samples exposed to picric acid or mercuric chloride containing fixatives was not intact. Increasing the formalin fixation time decreased the amount of intact DNA available. When these limitations were taken into consideration, the procedure allowed for the removal ofdegraded and chemically modified DNA from the preparation, and the final productwas suitable for quantitativeand qualitativeanalysis by Southern or dot blotting techniques. Digestion with methylation sensitive restriction endonucleases showed that DNA methylation pat term were not altered after formalin fixation. INTRODUCFION The field of molecular biology has expanded rapidly over the last few years, and a large amount of new information has accumulated on the organization of the human genome. The genome is not as static as previously thought, and gene rear rangement (1), amplification (2), deletion (3), mutation (4), and altered DNA methylation patterns (5, 6) are examples of deter minants now thought to be important for the regulation of gene expression. Similar modifications are also thought to take place in neoplastic processes and may have prognostic significance.
Wounds a Compendium of Clinical Research and Practice, 2004
Advances in Skin & Wound Care, 2015
Endocrine Abstracts, 2015
Ostomy/wound management, 2013
Clinicians treating pressure ulcers in the elderly in long-term care often face psychosocial, fin... more Clinicians treating pressure ulcers in the elderly in long-term care often face psychosocial, financial, and patient quality-of-life challenges; as such, they seek to identify products that meet wound healing goals as expeditiously as possible. The purpose of this case series was to evaluate outcomes of serial sharp debridement and the application of a formulated collagen gel in patients with chronic, nonhealing pressure ulcers. Three patients (two women ages 82 and 74 years of age and one man 82 years old, all incontinent of bladder and bowel with numerous comorbidities) had wounds >18 months' duration on the buttocks or coccyx that failed to improve despite the use of a wide variety of treatments, including negative pressure wound therapy. All wounds were debrided at the start of treatment and weekly thereafter if necessary, followed by application of the collagen gel. The gel was covered with a sterile bordered gauze and, if needed, a semipermeable dressing. Dressings were...
Molecular and cellular biology, 1994
Although loss of cell surface fibronectin (FN) is a hallmark of many oncogenically transformed ce... more Although loss of cell surface fibronectin (FN) is a hallmark of many oncogenically transformed cells, the mechanisms responsible for this phenomenon remain poorly understood. The present study utilized the nontumorigenic human osteosarcoma cell line TE-85 to investigate the effects of induced Ha-ras oncogene expression on FN biosynthesis. TE-85 cells were stably transfected with metallothionein-Ha-ras fusion genes, and the effects of metal-induced ras expression on FN biosynthesis were determined. Induction of the ras oncogene, but not proto-oncogene, was accompanied by a decrease in total FN mRNA and protein levels. Transfection experiments indicated that these oncogene effects were not due to reduced FN promoter activity, suggesting that a posttranscriptional mechanism was involved. The most common mechanism of posttranscriptional regulation affects cytoplasmic mRNA stability. However, in this study the down-regulation of FN was identified as a nuclear event. A component of the ra...
Wound Repair and Regeneration, 2011
We assessed the safety and efficacy of Formulated Collagen Gel (FCG) alone and with Ad5PDGF-B (GA... more We assessed the safety and efficacy of Formulated Collagen Gel (FCG) alone and with Ad5PDGF-B (GAM501) compared with Standard of Care (SOC) in patients with 1.5-10.0 cm 2 chronic diabetic neuropathic foot ulcers that healed < 30% during Run-in. Wound size was assessed by planimetry of acetate tracings and photographs in 124 patients. Comparison of data sets revealed that acetate tracings frequently overestimated areas at some sites. For per-protocol analysis, 113 patients qualified using acetate tracings but only 82 qualified using photographs. Prior animal studies suggested that collagen alone would have little effect on healing and would serve as a negative control. Surprisingly trends for increased incidence of complete closure were observed for both GAM501 (41%) and FCG (45%) vs. Standard of Care (31%). By photographic data, Standard of Care had no significant effect on change in wound radius (mm/week) from during Run-in to Week 1 (À0.06 AE 0.32 to 0.78 AE 1.53, p5ns) but both FCG (À0.08 AE 0.61 to 1.97 AE 1.77, p < 0.002) and GAM501 (À0.02 AE 0.58 to 1.46 AE 1.37, p < 0.002) significantly increased healing rates that gradually declined over subsequent weeks. Both GAM501 and FCG appeared to be safe and well tolerated, and alternate dosing schedules hold promise to improve overall complete wound closure in adequately powered trials.
Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research, 1991
The basal level of fibronectin (FN) biosynthesis is greatly reduced in N-ras-transformed human fi... more The basal level of fibronectin (FN) biosynthesis is greatly reduced in N-ras-transformed human fibrosarcoma HT1080 cells when compared with normal fibroblasts. The rate of FN biosynthesis can be significantly increased in HT1080 cells by the synthetic glucocorticoid dexamethasone, which has been shown to act by selectively stabilizing the FN message (D.C. Dean, R.F. Newby, and S. Bourgeois, J. Cell Biol., 106: 2159-2170, 1988). The present study demonstrates that the basal levels of FN biosynthesis and accumulated FN mRNA are also reduced in HT1080 cells when compared with nontumorigenic revertants of HT1080 cells in which the mutated N-ras allele is underrepresented. In contrast, the FN promoter is more active in HT1080 cells than in the revertant cells. These results indicate that the down-regulation of FN in HT1080 cells is linked to expression of the N-ras oncogene and that the effect is posttranscriptional. Therefore, the N-ras oncogene and glucocorticoids have opposite posttra...
The Molecular Biology of Cell Determination and Cell Differentiation, 1988
Although numerous possible functions of eukaryotic DNA methylation have been proposed (Ehrlich an... more Although numerous possible functions of eukaryotic DNA methylation have been proposed (Ehrlich and Wang, 1981), current evidence suggests an association between hypomethylation of specific gene regions and transcriptional activity (Doerfler, 1983; Riggs and Jones, 1983). Considerable excitement has been generated by the finding that potential methylation sites are often clustered at the 5&amp;#39; regions of genes (Bird et al., 1985). Furthermore, these clusters appear to be protected from methylation when associated with actively expressed genes. These findings have generated a new line of thinking among researchers, namely that genes may be regulated by domains of methylation sites (Jones, 1986). Although the evidence supporting a role for methylation in eukaryotic gene regulation is convincing, it is by no means unequivocal (Bird, 1984). To date, however, determination of the methylation status of specific cytosine residues in DNA has been limited by the experimental tools at hand. Therefore, development of a method that allows for evaluation of the methylation status of all CpG sites within, and in the vicinity of, genes may be necessary to elucidate the exact relationship between DNA methylation and gene expression. The emerging consensus is that DNA methylation is one component of a hierarchy of control mechanisms that regulate eukaryotic gene expression and cellular differentiation. Furthermore, the realization that methylation plays an important role in regulating gene expression during normal cellular differentiation suggests that aberrations in this potential controlling mechanism may be implicated in the abnormal gene expression seen in cancer. Indeed, a large body of experimental evidence demonstrates altered levels and patterns of methylation in tumor cells (Riggs and Jones, 1983; Jones, 1986). The regulatory function of 5-mCyt is most likely exerted via DNA-protein interactions. Two key questions remain unanswered: How does 5-mCyt affect these interactions? More importantly, what are the proteins that modulate DNA methylation during differentiation?
Wound Repair and Regeneration, 2009
The results from a Phase 1/2 study of a replication-defective adenovirus encoding human platelet-... more The results from a Phase 1/2 study of a replication-defective adenovirus encoding human platelet-derived growth factor (PDGF)-B formulated in a bovine collagen (Ad-5PDGF-B; 2.6% collagen; GAM501) gel for nonhealing neuropathic diabetic foot ulcers is reported. The primary objectives of the study were to evaluate the safety, maximum-tolerated dose, and preliminary biological activity of GAM501. Fifteen patients enrolled into the study with chronic, nonhealing ulcers received either a single administration of GAM501 at one of three dose levels, or up to four administrations of GAM501 at 1-week intervals. All patients received standard of care treatment including debridement and were required to wear an off-loading shoe. GAM501 was found to be safe and well tolerated with no evidence of systemic or local toxicity at all doses so no maximum-tolerated dose was reached. Serum antibody titers to platelet-derived growth factor-B homodimer and collagen were negative and adenoviral DNA was not detected in the blood. In the 12 patients that completed the study, ulcer closure was observed by Month 3 in 10 patients, seven of whom received a single application of GAM501. In conclusion, GAM501 did not appear to have any toxicity at doses that showed biological activity. GAM501 holds promise as a potentially effective treatment for nonhealing diabetic foot ulcers. Ad5-PDGF-B Adenovirus serotype 5 encoding PDGF-B DPN Diabetic peripheral neuropathy GAM Gene activated matrix GAM501 Ad5-PDGF-B in 2.6% collagen PCR Polymerase chain reaction PDGF-BB Platelet-derived growth factor-B homodimer SOC Standard of care vp Viral particle number