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Melanoma: HELP
Articles by J. Harrison Howard
Based on 6 articles published since 2008
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Between 2008 and 2019, J. Harrison Howard wrote the following 6 articles about Melanoma.
 
+ Citations + Abstracts
1 Review MicroRNA dysregulation in melanoma. 2016

Latchana, Nicholas / Ganju, Akaansha / Howard, J Harrison / Carson, William E. ·Department of Surgery, The Ohio State University, Columbus, OH 43210, USA. Electronic address: Nicholas.Latchana@osumc.edu. · Department of Surgery, The Ohio State University, Columbus, OH 43210, USA. Electronic address: Aganju@neomed.edu. · Department of Surgery, The Ohio State University, Columbus, OH 43210, USA. Electronic address: John.Howard@osumc.edu. · Department of Surgery, The Ohio State University, Columbus, OH 43210, USA; Department of Molecular Virology, Immunology and Medical Genetics, The Arthur G. James Comprehensive Cancer Center and Richard J. Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA. Electronic address: William.Carson@osumc.edu. ·Surg Oncol · Pubmed #27566021.

ABSTRACT: Melanoma is the deadliest form of skin cancer. Current challenges facing the management of melanoma include accurate prediction of individuals who will respond to adjuvant therapies as well as early detection of recurrences. These and other challenges have prompted investigation into biomarkers that could be used as diagnostic, prognostic and therapeutic aids. MicroRNAs (miRs) are small 19-22 nucleotide RNA inhibitors of protein translation. Over 800 different miRs are present within cells and importantly miR expression profiles may vary across different cells types and stages of malignancy. Unique expression profiles have been described for malignant melanoma; however, this work has yet to be translated into routine clinical practice. We highlight pertinent studies involving common miRs implicated in the oncogenesis of melanoma including miR-21, miR-125b, miR-150, miR-155, miR-205, and miR-211. In particular, emphasis is placed upon differential expression across different stages of melanoma progression, prognostic implications and potential mechanistic involvement. Focused efforts on inhibition of these miRs could be the most efficient method of translating preclinical endeavors into clinically meaningful applications.

2 Article Alterations in patient plasma microRNA expression profiles following resection of metastatic melanoma. 2018

Latchana, Nicholas / DiVincenzo, Mallory J / Regan, Kelly / Abrams, Zachary / Zhang, Xiaoli / Jacob, Naduparambil K / Gru, Alejandro A / Fadda, Paolo / Markowitz, Joseph / Howard, J Harrison / Carson, William E. ·Department of General Surgery, University of Toronto, Toronto, Canada. · Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio. · Medical Scientist Training Program and Biomedical Sciences Graduate Program, The Ohio State University, Columbus, Ohio. · Department of Biomedical Informatics, The Ohio State University, Columbus, Ohio. · Department of Radiation Oncology, The Ohio State University, Columbus, Ohio. · Department of Pathology, University of Virginia, Charlottesville, Virginia. · Department of Molecular Virology, Immunology and Medical Genetics, The Arthur G. James Comprehensive Cancer Center and Richard J. Solove Research Institute, The Ohio State University, Columbus, Ohio. · Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, Florida. · Department of Surgery, The Ohio State University, Columbus, Ohio. ·J Surg Oncol · Pubmed #30132912.

ABSTRACT: BACKGROUND AND OBJECTIVES: MicroRNAs (miRs) are noncoding RNAs that regulate protein translation and melanoma progression. Changes in plasma miR expression following surgical resection of metastatic melanoma are under-investigated. We hypothesize differences in miR expression exist following complete surgical resection of metastatic melanoma. METHODS: Blood collection pre- and post-surgical resection was performed in six individuals with solitary melanoma metastases. miR expression in extracted RNA was quantified using the NanoString nCounter Digital Analyzer. RESULTS: Pre- and post-surgical plasma samples contained 216 miRs with expression above baseline. Comparison of postsurgical to preresection samples revealed differential expression of 25 miRs: miR-let-7a, miR-let7g, miR-15a, miR-16, miR-22, miR-30b, miR-126, miR-140, miR-145, miR-148a, miR-150-5p, miR-191, miR-378i, miR-449c, miR-494, miR-513b, miR-548aa, miR-571, miR-587, miR-891b, miR-1260a, miR 1268a, miR-1976, miR-4268, miR-4454 (P < 0.05). Utilizing P < 0.0046 as a cutoff to control for one false positive among the 216 miRs revealed that postsurgical melanoma plasma samples had upregulation of miR-1260a (P = 0.0007) and downregulation of miR-150-5p (P = 0.0026) relative to pre-surgical samples. CONCLUSIONS: Differential expression of miR-150-5p and miR-1260a is present in plasma following surgical resection of metastatic melanoma in this small sample (n = 6) of melanoma patients. Therefore, further investigation of these plasma miRs as noninvasive biomarkers for melanoma is warranted.

3 Article Surveillance strategies in the follow-up of melanoma patients: too much or not enough? 2017

Kurtz, James / Beasley, Georgia M / Agnese, Doreen / Kendra, Kari / Olencki, Thomas E / Terando, Alicia / Howard, J Harrison. ·Department of Surgery, Doctors Hospital, Columbus, Ohio. Electronic address: james.kurtz@ohiohealth.com. · Division of Surgical Oncology, Ohio State University Wexner Medical Center, Columbus, Ohio. · Division of Medical Oncology, Ohio State University Wexner Medical Center, Columbus, Ohio. ·J Surg Res · Pubmed #28624057.

ABSTRACT: BACKGROUND: After appropriate initial therapy for patients with stage II-III melanoma, there is no consensus regarding surveillance. Thus, follow-up is highly variable among institutions and individual providers. The National Comprehensive Cancer Network recommends routine clinical examination and consideration of imaging for stage IIB-IIIC every 3-12 mo with no distinction between stages. Detection of recurrence is important as novel systemic therapies and surgical resection of recurrence may provide survival benefits. METHODS: We retrospectively reviewed 369 patients with stage II and III melanoma treated at Ohio State University from 2009-2015, who underwent surgery as primary therapy. Two hundred forty-seven patients who were followed for a minimum of 6 mo after surgical resection to achieve no evidence of disease status (NED) were included in this analysis. One hundred twenty-two were lost to follow-up after surgery and were excluded. RESULTS: The rate of recurrence for stage IIA/IIB patients was 11% (14/125). Eleven of the 14 (79%) recurrences were detected by clinical symptoms or physical examination. Thirty-nine percent (49/125) of stage IIA or IIB patients were followed by clinical examination only, whereas 61% (76/125) were followed with at least two serial chest x-rays. The median time to first chest x-ray after NED status was 4.7 mo (n = 76), median time to second chest x-ray after NED status was 12.7 mo (n = 76), and 66% (50/76) continued to have additional serial chest x-rays. At median follow-up of 35 mo for the 125 patients with stage IIA/IIB, there was no difference in survival between those followed clinically (95% [95% CI: 0.88-0.99]) versus those followed with at least two serial x-rays (96% [95% CI: 0.89-0.98]). For stage IIC/IIIA-C patients, recurrence was detected in 23% (28/122) at median follow-up 31.2 mo. Fifty percent of recurrences were detected by imaging in asymptomatic patients, whereas 50% (14/28) had recurrence detected on imaging associated clinical findings. Eighty-seven percent (106/122) of stage IIC/IIIA-C patients were followed with at least two serial whole body positron emission tomography/computed tomography (CT) scans or whole body CT scans plus brain magnetic resonance imaging; median time between NED status and second scan was 10.3 mo. Of stage IIC/IIIA-C patients with recurrence, 57% (16/28) went on to surgical resection of the recurrence, whereas 11 (39%) patients received B-RAF inhibitor therapy, immune blockade therapy, or combination therapy. CONCLUSIONS: For stage IIA and IIB melanoma, surveillance chest x-rays did not improve survival compared to physical examination alone. However, for stage IIC and IIIA-C melanoma, where the recurrence rates are higher, routine whole body imaging detected 50% of recurrences leading to additional surgery and/or treatment with novel systemic therapies for the majority of patients. Detection of melanoma recurrence is important and specific substage should be used to stratify risk and define appropriate follow-up.

4 Article Sentinel Lymph Node Biopsy for Recurrent Melanoma: A Multicenter Study. 2017

Beasley, Georgia M / Hu, Yinin / Youngwirth, Linda / Scheri, Randall P / Salama, April K / Rossfeld, Kara / Gardezi, Syed / Agnese, Doreen M / Howard, J Harrison / Tyler, Douglas S / Slingluff, Craig L / Terando, Alicia M. ·Division of Surgical Oncology, Ohio State University Wexner Medical Center, Columbus, OH, USA. Georgia.beasley@osumc.edu. · Division of Surgical Oncology, University of Virginia, Charlottesville, VA, USA. · Department of Surgery, Duke University, Durham, NC, USA. · Division of Medical Oncology, Duke University, Durham, NC, USA. · Division of Surgical Oncology, Ohio State University Wexner Medical Center, Columbus, OH, USA. · Department of Surgery, University of Texas Medical Branch, Galveston, TX, USA. ·Ann Surg Oncol · Pubmed #28508145.

ABSTRACT: BACKGROUND: Sentinel lymph node biopsy (SLNB) is routinely performed for primary cutaneous melanomas; however, limited data exist for SLNB after locally recurrent (LR) or in-transit (IT) melanoma. METHODS: Data from three centers performing SLNB for LR/IT melanoma (1997 to the present) were reviewed, with the aim of assessing (1) success rate; (2) SLNB positivity; and (3) prognostic value of SLNB in this population. RESULTS: The study cohort included 107 patients. Management of the primary melanoma included prior SLNB for 56 patients (52%), of whom 10 (18%) were positive and 12 had complete lymph node dissections (CLNDs). In the present study, SLNB was performed for IT disease (48/107, 45%) or LR melanoma (59/107, 55%). A sentinel lymph node (SLN) was removed in 96% (103/107) of cases. Nodes were not removed for four patients due to lymphoscintigraphy failures (2) or nodes not found during surgery (2). SLNB was positive in 41 patients (40%, 95% confidence interval (CI) 31.5-50.5), of whom 35 (88%) had CLND, with 13 (37%) having positive nonsentinel nodes. Median time to disease progression after LR/IT metastasis was 1.4 years (95% CI 0.75-2.0) for patients with a positive SLNB, and 5.9 years (95% CI 1.7-10.2) in SLNB-negative patients (p = 0.18). There was a trend towards improved overall survival for patients with a negative SLNB (p = 0.06). CONCLUSION: SLNB can be successful in patients with LR/IT melanoma, even if prior SLNB was performed. In this population, the rates of SLNB positivity and nonsentinel node metastases were 40% and 37%, respectively. SLNB may guide management and prognosis after LR/IT disease.

5 Article Classification of Indeterminate Melanocytic Lesions by MicroRNA Profiling. 2017

Latchana, Nicholas / Del Campo, Sara E Martin / Grignol, Valerie P / Clark, Jennifer R / Albert, Scott P / Zhang, Jie / Wei, Lai / Aldrink, Jennifer H / Nicol, Kathleen K / Ranalli, Mark A / Peters, Sara B / Gru, Alejandro / Trihka, Prashant / Payne, Philip R O / Howard, J Harrison / Carson, William E. ·Department of Surgery, The Ohio State University, Columbus, OH, USA. · Department of Internal Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. · Department of Surgery, Upstate University Hospital, Syracuse, NY, USA. · Department of Biomedical Informatics, The Ohio State University, Columbus, OH, USA. · Department of Pediatric Surgery, Nationwide Children's Hospital, Columbus, OH, USA. · Department of Pathology, Nationwide Children's Hospital, Columbus, OH, USA. · Department of Hematology/Oncology, Nationwide Children's Hospital, Columbus, OH, USA. · Department of Pathology, The Ohio State University, Columbus, OH, USA. · Department of Pathology, University of Virginia, Charlottesville, VA, USA. · Department of Molecular Virology, Immunology and Medical Genetics, The Arthur G. James Comprehensive Cancer Center and Richard J. Solove Research Institute, The Ohio State University, Columbus, OH, USA. · Institute of Informatics, Washington University, St. Louis, MO, USA. · Department of Surgery, The Ohio State University, Columbus, OH, USA. William.Carson@osumc.edu. · Department of Molecular Virology, Immunology and Medical Genetics, The Arthur G. James Comprehensive Cancer Center and Richard J. Solove Research Institute, The Ohio State University, Columbus, OH, USA. William.Carson@osumc.edu. ·Ann Surg Oncol · Pubmed #27469124.

ABSTRACT: PURPOSE: Identification of indeterminate melanocytic skin lesions capable of neoplastic progression is suboptimal and may potentially result in unnecessary morbidity from surgery. MicroRNAs (miRs) may be useful in classifying indeterminate Spitz tumors as having high or low risk for malignant behavior. METHODS: RNA was extracted from paraffin-embedded tissues of benign nevi, benign Spitz tumors, indeterminate Spitz tumors, and Spitzoid melanomas in adults (n = 62) and children (n = 28). The expression profile of 12 miRs in adults (6 miRs in children) was analyzed by real-time polymerase chain reaction. RESULTS: Benign Spitz lesions were characterized by decreased expression of miR-125b and miR-211, and upregulation of miR-22, compared with benign nevi (p < 0.05). A comparison of Spitzoid melanomas to benign nevi revealed overexpression of miR-21, miR-150, and miR-155 in the malignant primaries (p < 0.05). In adults, Spitzoid melanomas exhibited upregulation of miR-21, miR-150, and miR-155 compared with indeterminate Spitz lesions. Indeterminate Spitz lesions with low-risk pathologic features had lower miR-21 and miR-155 expression compared with Spitzoid melanoma tumors in adults (p < 0.05), while pathologic high-risk indeterminate Spitz lesions had increased levels of miR-200c expression compared with low-risk indeterminate lesions (p < 0.05). Pediatric Spitzoid melanomas exhibited increased miR-21 expression compared with indeterminate Spitz lesions (p < 0.05). Moreover, miR-155 expression was increased in indeterminate lesions with mitotic counts >1 and depth of invasion >1 mm, suggesting miR-155 expression is associated with histological characteristics. CONCLUSIONS: miR expression profiles can be measured in indeterminate Spitz tumors and correlate with markers of malignant potential.

6 Article Metastasectomy for distant metastatic melanoma: analysis of data from the first Multicenter Selective Lymphadenectomy Trial (MSLT-I). 2012

Howard, J Harrison / Thompson, John F / Mozzillo, Nicola / Nieweg, Omgo E / Hoekstra, Harald J / Roses, Daniel F / Sondak, Vernon K / Reintgen, Douglas S / Kashani-Sabet, Mohammed / Karakousis, Constantine P / Coventry, Brendon J / Kraybill, William G / Smithers, B Mark / Elashoff, Robert / Stern, Stacey L / Cochran, Alistair J / Faries, Mark B / Morton, Donald L. ·Department of Surgical Oncology, John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, CA, USA. ·Ann Surg Oncol · Pubmed #22648554.

ABSTRACT: BACKGROUND: For stage IV melanoma, systemic medical therapy (SMT) is used most frequently; surgery is considered an adjunct in selected patients. We retrospectively compared survival after surgery with or without SMT versus SMT alone for melanoma patients developing distant metastases while enrolled in the first Multicenter Selective Lymphadenectomy Trial. METHODS: Patients were randomized to wide excision and sentinel node biopsy, or wide excision and nodal observation. We evaluated recurrence site, therapy (selected by treating clinician), and survival after stage IV diagnosis. RESULTS: Of 291 patients with complete data for stage IV recurrence, 161 (55 %) underwent surgery with or without SMT. Median survival was 15.8 versus 6.9 months, and 4-year survival was 20.8 versus 7.0 % for patients receiving surgery with or without SMT versus SMT alone (p < 0.0001; hazard ratio 0.406). Surgery with or without SMT conferred a survival advantage for patients with M1a (median > 60 months vs. 12.4 months; 4-year survival 69.3 % vs. 0; p = 0.0106), M1b (median 17.9 vs. 9.1 months; 4-year survival 24.1 vs. 14.3 %; p = 0.1143), and M1c (median 15.0 vs. 6.3 months; 4-year survival 10.5 vs. 4.6 %; p = 0.0001) disease. Patients with multiple metastases treated surgically had a survival advantage, and number of operations did not reduce survival in the 67 patients (42 %) who had multiple surgeries for distant melanoma. CONCLUSIONS: Our findings suggest that over half of stage IV patients are candidates for resection and exhibit improved survival over patients receiving SMT alone, regardless of site and number of metastases. We have begun a multicenter randomized phase III trial comparing surgery versus SMT as initial treatment for resectable distant melanoma.