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Prof. Seongho Kim
Wayne State University School of Medicine, Detroit, United States

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0 Cancer Metabolomics
0 High-throughput data analysis
0 Pharmacokinetics/Pharmacodynamics (PK/PD)
0 Clinical trial designs
0 Computational/statistical biology

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Journal article
Published: 24 August 2021 in Vaccines
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Background: Vaccine hesitancy is the next great barrier for public health. Arab Americans are a rapidly growing demographic in the United States with limited information on the prevalence of vaccine hesitancy. We therefore sought to study the attitudes towards the coronavirus disease 2019 (COVID-19) vaccine amongst Arab American health professionals living in the United States. Methods: This was a cross sectional study utilizing an anonymous online survey. The survey was distributed via e-mail to National Arab American Medical Association members and Arab-American Center for Economic and Social Services healthcare employees. Respondents were considered vaccine hesitant if they selected responses other than a willingness to receive the COVID-19 vaccine. Results: A total of 4000 surveys were sent via e-mail from 28 December 2020 to 31 January 2021, and 513 responses were received. The highest group of respondents were between the ages of 18–29 years and physicians constituted 48% of the respondents. On multivariable analysis, we found that respondents who had declined an influenza vaccine in the preceding 5 years (p< 0.001) and allied health professionals (medical assistants, hospital administrators, case managers, researchers, scribes, pharmacists, dieticians and social workers) were more likely to be vaccine hesitant (p = 0.025). In addition, respondents earning over $150,000 US dollars annually were less likely to be vaccine hesitant and this finding was significant on multivariable analysis (p = 0.011). Conclusions: Vaccine hesitancy among health care providers could have substantial impact on vaccine attitudes of the general population, and such data may help inform vaccine advocacy efforts.

ACS Style

Anita Shallal; Evi Abada; Rami Musallam; Omar Fehmi; Linda Kaljee; Ziad Fehmi; Suma Alzouhayli; Deema Ujayli; Doreen Dankerlui; Seongho Kim; Michele L. Cote; Vijaya Arun Kumar; Marcus Zervos; Rouba Ali-Fehmi. Evaluation of COVID-19 Vaccine Attitudes among Arab American Healthcare Professionals Living in the United States. Vaccines 2021, 9, 942 .

AMA Style

Anita Shallal, Evi Abada, Rami Musallam, Omar Fehmi, Linda Kaljee, Ziad Fehmi, Suma Alzouhayli, Deema Ujayli, Doreen Dankerlui, Seongho Kim, Michele L. Cote, Vijaya Arun Kumar, Marcus Zervos, Rouba Ali-Fehmi. Evaluation of COVID-19 Vaccine Attitudes among Arab American Healthcare Professionals Living in the United States. Vaccines. 2021; 9 (9):942.

Chicago/Turabian Style

Anita Shallal; Evi Abada; Rami Musallam; Omar Fehmi; Linda Kaljee; Ziad Fehmi; Suma Alzouhayli; Deema Ujayli; Doreen Dankerlui; Seongho Kim; Michele L. Cote; Vijaya Arun Kumar; Marcus Zervos; Rouba Ali-Fehmi. 2021. "Evaluation of COVID-19 Vaccine Attitudes among Arab American Healthcare Professionals Living in the United States." Vaccines 9, no. 9: 942.

Journal article
Published: 23 June 2021 in Transplantation and Cellular Therapy
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: Limited information is available on the efficacy of post-transplant cyclophosphamide (PTcy) or thymoglobulin for GVHD prophylaxis in mismatched unrelated donor (MMUD) transplants. : We retrospectively compared outcomes of 76 adult AML and MDS patients who underwent 7/8 HLA-MMUD transplants and received either PTcy (50 mg/kg on day +3 and +4) or thymoglobulin (total dose 4.5 mg/kg) for GVHD prophylaxis. In addition, tacrolimus and mycophenolate were used in both groups. Propensity score-based multivariable analyses (PSCA) were performed to adjust confounding effects of patient characteristics between both groups. : Between January 2006 and June 2019, 25 patients received PTcy and 51 received thymoglobulin. Median age of the population was 57 years, 78% of patients had AML, most common graft source was peripheral blood (96%), and 46% received myeloablative conditioning regimens. Median time to neutrophil (15 versus 11 days, p<0.001) and platelet engraftment (21 versus 15 days, p=0.002) was prolonged in the PTcy group. The cumulative incidence of grade III-IV acute GVHD at day 100 was similar (12% versus 19.6%, p=0.38), while chronic GVHD at 1-year was lower with PTcy compared to thymoglobulin (16% versus 49%, p=0.006). Using PSCA, no difference in survival, relapse, relapse-free survival, and GVHD-free relapse-free survival was seen between groups. However, thymoglobulin was associated with higher incidence of acute (HR 2.63, p=0.01) and chronic GVHD (HR 4.43, p=0.03), and non-relapse mortality (HR 3.38, p=0.04) compared to PTcy. : Our study demonstrated that PTcy resulted in significantly lower rates of acute and chronic GVHD, and non-relapse mortality compared to thymoglobulin in 7/8 HLA-MMUD transplants for AML and MDS.

ACS Style

Dipenkumar Modi; Kyle Kondrat; Seongho Kim; Abhinav Deol; Lois Ayash; Voravit Ratanatharathorn; Joseph P. Uberti. Post-transplant Cyclophosphamide Versus Thymoglobulin in HLA-Mismatched Unrelated Donor Transplant for Acute Myelogenous Leukemia and Myelodysplastic Syndrome. Transplantation and Cellular Therapy 2021, 27, 760 -767.

AMA Style

Dipenkumar Modi, Kyle Kondrat, Seongho Kim, Abhinav Deol, Lois Ayash, Voravit Ratanatharathorn, Joseph P. Uberti. Post-transplant Cyclophosphamide Versus Thymoglobulin in HLA-Mismatched Unrelated Donor Transplant for Acute Myelogenous Leukemia and Myelodysplastic Syndrome. Transplantation and Cellular Therapy. 2021; 27 (9):760-767.

Chicago/Turabian Style

Dipenkumar Modi; Kyle Kondrat; Seongho Kim; Abhinav Deol; Lois Ayash; Voravit Ratanatharathorn; Joseph P. Uberti. 2021. "Post-transplant Cyclophosphamide Versus Thymoglobulin in HLA-Mismatched Unrelated Donor Transplant for Acute Myelogenous Leukemia and Myelodysplastic Syndrome." Transplantation and Cellular Therapy 27, no. 9: 760-767.

Journal article
Published: 12 May 2021 in Transplantation and Cellular Therapy
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Fludarabine 30 mg/m2/day x 5 and melphalan 140 mg/m2 x 1 (Flu-Mel140) is a commonly used RIC regimen. We hypothesized that addition of 200cGy total body irradiation (TBI) to Flu-Mel140 may improve antitumor activity and transplant outcomes. Primary objectives was overall survival (OS) at 3-year. Secondary objectives were to assess the cumulative incidences of acute and chronic GVHD, relapse-free survival (RFS), relapse rate, and non-relapse mortality (NRM). We retrospectively evaluated outcomes of patients receiving Flu-Mel140-TBI followed by HLA-matched donor allogeneic hematopoietic stem cell transplantation (alloSCT) using peripheral blood stem cells. Eighty-one patients (median age, 58 years) underwent alloSCT between January 2008 and December 2018. Thirty-one percent patients had prior transplant, 32% had high or very-high disease risk index, and the donor was unrelated in 70% of patients. Grade 3-4 regimen-related toxicities were mucositis (37%), cardiac toxicity (17%), and renal toxicity (10%). The cumulative incidence of grade III-IV acute GVHD at day +100 was 24.7% and chronic GVHD at 1-year was 51.3%. Median follow-up for survival was 6.1 years. At 3-year, overall survival (OS) was 39.81%, RFS was 31.47%, and relapse rate was 30.5%. One-year NRM was 29.9%. Patients undergoing first transplant experienced improved OS compared to second or beyond (63.08% vs 42.31%, p=0.02). After adjusting for disease subtypes, age (≤55 vs 55), comorbidity index (CI), number of transplant and GVHD prophylaxis, multivariable analysis did not demonstrate any survival difference among disease subtypes. High CI (≥3) was predictive of adverse OS and NRM, while older age (>55 years) was associated with high NRM. Our study shows that Flu-Mel140-TBI seems feasible, and provides durable disease control. Addition of TBI did not appear to improve outcomes compared to previously published reports of Flu-Mel140. Considerable NRM could result from the inclusion of patients with older age and prior transplants.

ACS Style

Dipenkumar Modi; Jie Chi; Seongho Kim; Abhinav Deol; Lois Ayash; Voravit Ratanatharathorn; Joseph P. Uberti. Outcomes of Fludarabine, Melphalan and Total Body Irradiation as a Reduced Intensity Conditioning Regimen in Matched Donor Allogeneic Peripheral Blood Stem Cell Transplantation. Transplantation and Cellular Therapy 2021, 1 .

AMA Style

Dipenkumar Modi, Jie Chi, Seongho Kim, Abhinav Deol, Lois Ayash, Voravit Ratanatharathorn, Joseph P. Uberti. Outcomes of Fludarabine, Melphalan and Total Body Irradiation as a Reduced Intensity Conditioning Regimen in Matched Donor Allogeneic Peripheral Blood Stem Cell Transplantation. Transplantation and Cellular Therapy. 2021; ():1.

Chicago/Turabian Style

Dipenkumar Modi; Jie Chi; Seongho Kim; Abhinav Deol; Lois Ayash; Voravit Ratanatharathorn; Joseph P. Uberti. 2021. "Outcomes of Fludarabine, Melphalan and Total Body Irradiation as a Reduced Intensity Conditioning Regimen in Matched Donor Allogeneic Peripheral Blood Stem Cell Transplantation." Transplantation and Cellular Therapy , no. : 1.

Journal article
Published: 10 March 2021 in Cancers
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Despite recent advances in therapeutic modalities such as radiochemotherapy, the long-term prognosis for patients with advanced head and neck squamous cell carcinoma (HNSCC), especially nonviral HNSCC, remains very poor, while survival of patients with human papillomavirus (HPV)-associated HNSCC is greatly improved after radiotherapy. The goal of this study is to develop a mechanism-based treatment protocol for high-risk patients with HPV-negative HNSCC. To achieve our goal, we have investigated molecular mechanisms underlying differential radiation sensitivity between HPV-positive and -negative HNSCC cells. Here, we found that autophagy is associated with radioresistance in HPV-negative HNSCC, whereas apoptosis is associated with radiation sensitive HPV-positive HNSCC. Interestingly, we found that photodynamic therapy (PDT) directed at the endoplasmic reticulum (ER)/mitochondria initially induces paraptosis followed by apoptosis. This led to a substantial increase in radiation responsiveness in HPV-negative HNSCC, while the same PDT treatment had a minimal effect on HPV-positive cells. Here, we provide evidence that the autophagic adaptor p62 mediates signal relay for the induction of apoptosis, promoting ionizing radiation (XRT)-induced cell death in HPV-negative HNSCC. This work proposes that ER/mitochondria-targeted PDT can serve as a radiosensitizer in intrinsically radioresistant HNSCC that exhibits an increased autophagic flux.

ACS Style

Won Cho; David Kessel; Joseph Rakowski; Brian Loughery; Abdo Najy; Tri Pham; Seongho Kim; Yong Kwon; Ikuko Kato; Harold Kim; Hyeong-Reh Kim. Photodynamic Therapy as a Potent Radiosensitizer in Head and Neck Squamous Cell Carcinoma. Cancers 2021, 13, 1193 .

AMA Style

Won Cho, David Kessel, Joseph Rakowski, Brian Loughery, Abdo Najy, Tri Pham, Seongho Kim, Yong Kwon, Ikuko Kato, Harold Kim, Hyeong-Reh Kim. Photodynamic Therapy as a Potent Radiosensitizer in Head and Neck Squamous Cell Carcinoma. Cancers. 2021; 13 (6):1193.

Chicago/Turabian Style

Won Cho; David Kessel; Joseph Rakowski; Brian Loughery; Abdo Najy; Tri Pham; Seongho Kim; Yong Kwon; Ikuko Kato; Harold Kim; Hyeong-Reh Kim. 2021. "Photodynamic Therapy as a Potent Radiosensitizer in Head and Neck Squamous Cell Carcinoma." Cancers 13, no. 6: 1193.

Journal article
Published: 16 February 2021 in Annals of Hematology
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A head-to-head comparison of outcomes of unrelated donor allogeneic peripheral blood stem cell transplantation for AML between reduced intensity conditioning (RIC) and myeloablative conditioning (MAC) regimens using thymoglobulin for GVHD prophylaxis is limited. We evaluated outcomes of 122 AML patients who received either busulfan (Bu)/fludarabine (Flu)/low-dose total body irradiation (TBI) as RIC (n = 64, 52%) or Bu/Flu as MAC (n = 58, 48%), and thymoglobulin 4.5 mg/kg total dose between day − 3 to − 1 for GVHD prophylaxis. Grades III–IV acute GVHD (aGVHD) was lower with Bu/Flu/TBI compared with Bu/Flu (6.2% vs 26.1%, p = 0.009). At 1 year, Bu/Flu/TBI was associated with similar chronic GVHD (41.2% vs 44.8%, p = 0.75), OS (61.9% vs 56.9%, p = 0.69), relapse rate (29.9% vs 20.7%, p = 0.24), relapse-free survival (52.8% vs 50%, p = 0.80), non-relapse mortality (17.4% vs 29.3%, p = 0.41), and GVHD-free relapse-free survival (24.2% vs 27.5%, p = 0.80) compared with Bu/Flu. Multivariable analysis did not reveal any difference in outcomes between both regimens. In summary, thymoglobulin at 4.5 mg/kg did not have any adverse impact on survival when used with RIC regimen. Both Bu/Flu/TBI and Bu/Flu conditioning regimens yielded similar survival.

ACS Style

Dipenkumar Modi; Vijendra Singh; Seongho Kim; Lois Ayash; Abhinav Deol; Voravit Ratanatharathorn; Joseph P. Uberti. Comparison of myeloablative and reduced intensity conditioning unrelated donor allogeneic peripheral blood stem cell transplant outcomes for AML using thymoglobulin for GVHD prophylaxis. Annals of Hematology 2021, 100, 969 -978.

AMA Style

Dipenkumar Modi, Vijendra Singh, Seongho Kim, Lois Ayash, Abhinav Deol, Voravit Ratanatharathorn, Joseph P. Uberti. Comparison of myeloablative and reduced intensity conditioning unrelated donor allogeneic peripheral blood stem cell transplant outcomes for AML using thymoglobulin for GVHD prophylaxis. Annals of Hematology. 2021; 100 (4):969-978.

Chicago/Turabian Style

Dipenkumar Modi; Vijendra Singh; Seongho Kim; Lois Ayash; Abhinav Deol; Voravit Ratanatharathorn; Joseph P. Uberti. 2021. "Comparison of myeloablative and reduced intensity conditioning unrelated donor allogeneic peripheral blood stem cell transplant outcomes for AML using thymoglobulin for GVHD prophylaxis." Annals of Hematology 100, no. 4: 969-978.

Journal article
Published: 25 August 2020 in Metabolites
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Untargeted metabolomics is expected to lead to a better mechanistic understanding of diseases and thus applications of precision medicine and personalized intervention. To further increase metabolite coverage and achieve high accuracy of metabolite quantification, the present proof-of-principle study was to explore the applicability of integration of two-dimensional gas and liquid chromatography-mass spectrometry (GC × GC-MS and 2DLC-MS) platforms to characterizing circulating polar metabolome extracted from plasma collected from 29 individuals with colorectal cancer in comparison with 29 who remained cancer-free. After adjustment of multiple comparisons, 20 metabolites were found to be up-regulated and 8 metabolites were found to be down-regulated, which pointed to the dysregulation in energy metabolism and protein synthesis. While integrating the GC × GC-MS and 2DLC-MS data can dramatically increase the metabolite coverage, this study had a limitation in analyzing the non-polar metabolites. Given the small sample size, these results need to be validated with a larger sample size and with samples collected prior to diagnostic and treatment. Nevertheless, this proof-of-principle study demonstrates the potential applicability of integration of these advanced analytical platforms to improve discrimination between colorectal cancer cases and controls based on metabolite profiles in future studies.

ACS Style

Fang Yuan; Seongho Kim; Xinmin Yin; Xiang Zhang; Ikuko Kato. Integrating Two-Dimensional Gas and Liquid Chromatography-Mass Spectrometry for Untargeted Colorectal Cancer Metabolomics: A Proof-of-Principle Study. Metabolites 2020, 10, 343 .

AMA Style

Fang Yuan, Seongho Kim, Xinmin Yin, Xiang Zhang, Ikuko Kato. Integrating Two-Dimensional Gas and Liquid Chromatography-Mass Spectrometry for Untargeted Colorectal Cancer Metabolomics: A Proof-of-Principle Study. Metabolites. 2020; 10 (9):343.

Chicago/Turabian Style

Fang Yuan; Seongho Kim; Xinmin Yin; Xiang Zhang; Ikuko Kato. 2020. "Integrating Two-Dimensional Gas and Liquid Chromatography-Mass Spectrometry for Untargeted Colorectal Cancer Metabolomics: A Proof-of-Principle Study." Metabolites 10, no. 9: 343.

Research article
Published: 28 March 2020 in Journal of Chemometrics
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The peak alignment is a vital preprocessing step before downstream analysis, such as biomarker discovery and pathway analysis, for two‐dimensional gas chromatography mass spectrometry (2DGCMS)–based metabolomics data. Due to uncontrollable experimental conditions, for example, the differences in temperature or pressure, matrix effects on samples, and stationary phase degradation, a shift of retention times among samples inevitably occurs during 2DGCMS experiments, making it difficult to align peaks. Various peak alignment algorithms have been developed to correct retention time shifts for homogeneous, heterogeneous, or both types of mass spectrometry data. However, almost all existing algorithms have been focused on a local alignment and are suffering from low accuracy especially when aligning dense biological data with many peaks. We have developed four global peak alignment (GPA) algorithms using coherent point drift (CPD) point matching algorithms: retention time‐based CPD‐GPA (RT), prior CPD‐GPA (P), mixture CPD‐GPA (M), and prior mixture CPD‐GPA (P + M). Method RT performs the peak alignment based only on the retention time distance, while methods P, M, and P + M carry out the peak alignment using both the retention time distance and mass spectral similarity. Method P incorporates the mass spectral similarity through prior information, and Methods M and P + M use the mixture distance measure. Four developed algorithms are applied to homogeneous and heterogeneous spiked‐in data as well as two real biological data and compared with three existing algorithms, mSPA, SWPA, and BiPACE‐2D. The results show that our CPD‐GPA algorithms perform better than all existing algorithms in terms of F1 score.

ACS Style

Zeyu Li; Seongho Kim; Sikai Zhong; Zichun Zhong; Ikuko Kato; Xiang Zhang. Coherent point drift peak alignment algorithms using distance and similarity measures for two‐dimensional gas chromatography mass spectrometry data. Journal of Chemometrics 2020, 34, e3236 .

AMA Style

Zeyu Li, Seongho Kim, Sikai Zhong, Zichun Zhong, Ikuko Kato, Xiang Zhang. Coherent point drift peak alignment algorithms using distance and similarity measures for two‐dimensional gas chromatography mass spectrometry data. Journal of Chemometrics. 2020; 34 (8):e3236.

Chicago/Turabian Style

Zeyu Li; Seongho Kim; Sikai Zhong; Zichun Zhong; Ikuko Kato; Xiang Zhang. 2020. "Coherent point drift peak alignment algorithms using distance and similarity measures for two‐dimensional gas chromatography mass spectrometry data." Journal of Chemometrics 34, no. 8: e3236.

Journal article
Published: 01 November 2019 in Cells
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Rad6B, a principal component of the translesion synthesis pathway, and activator of canonical Wnt signaling, plays an essential role in cutaneous melanoma development and progression. As Rad6 is encoded by two genes, namely, UBE2A (RAD6A) and UBE2B (RAD6B), in humans, we compared their expressions in melanomas and normal melanocytes. While both genes are weakly expressed in normal melanocytes, Rad6B is more robustly expressed in melanoma lines and patient-derived metastatic melanomas than RAD6A. The characterization of RAD6B transcripts revealed coexpression of various splice variants representing truncated or modified functional versions of wild-type RAD6B in melanomas, but not in normal melanocytes. Notably, two RAD6B isoforms with intact catalytic domains, RAD6BΔexon4 and RAD6Bintron5ins, were identified. We confirmed that RAD6BΔexon4 and RAD6Bintron5ins variants are expressed as 14 and 15 kDa proteins, respectively, with functional in vivo ubiquitin conjugating activity. Whole exome sequence analysis of 30 patient-derived melanomas showed RAD6B variants coexpressed with wild-type RAD6B in all samples analyzed, and RAD6Bintron5ins variants were found in half the cases. These variants constitute the majority of the RAD6B transcriptome in contrast to RAD6A, which was predominantly wild-type. The expression of functional RAD6B variants only in melanomas reveals RAD6B’s molecular heterogeneity and its association with melanoma pathogenesis.

ACS Style

Ambikai Gajan; Carly E. Martin; Seongho Kim; Milap Joshi; Sharon K. Michelhaugh; Ido Sloma; Sandeep Mittal; Steven Firestine; Malathy P. V. Shekhar; Kim. Alternative Splicing of RAD6B and Not RAD6A is Selectively Increased in Melanoma: Identification and Functional Characterization. Cells 2019, 8, 1375 .

AMA Style

Ambikai Gajan, Carly E. Martin, Seongho Kim, Milap Joshi, Sharon K. Michelhaugh, Ido Sloma, Sandeep Mittal, Steven Firestine, Malathy P. V. Shekhar, Kim. Alternative Splicing of RAD6B and Not RAD6A is Selectively Increased in Melanoma: Identification and Functional Characterization. Cells. 2019; 8 (11):1375.

Chicago/Turabian Style

Ambikai Gajan; Carly E. Martin; Seongho Kim; Milap Joshi; Sharon K. Michelhaugh; Ido Sloma; Sandeep Mittal; Steven Firestine; Malathy P. V. Shekhar; Kim. 2019. "Alternative Splicing of RAD6B and Not RAD6A is Selectively Increased in Melanoma: Identification and Functional Characterization." Cells 8, no. 11: 1375.

Correspondence
Published: 15 June 2019 in Leukemia Research
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Allogeneic stem cell transplant is a viable treatment in peripheral T-cell lymphoma Non-relapse mortality is substantial A few patients attain a durable response indicating graft versus lymphoma effect Patients with prior autologous transplant should be offered allogeneic transplant

ACS Style

Dipenkumar Modi; Malini Surapaneni; Seongho Kim; Lois Ayash; Asif Alavi; Voravit Ratanatharathorn; Abhinav Deol; Joseph P. Uberti. Allogeneic stem cell transplant provides durable response in peripheral T-cell lymphoma. Leukemia Research 2019, 83, 106171 .

AMA Style

Dipenkumar Modi, Malini Surapaneni, Seongho Kim, Lois Ayash, Asif Alavi, Voravit Ratanatharathorn, Abhinav Deol, Joseph P. Uberti. Allogeneic stem cell transplant provides durable response in peripheral T-cell lymphoma. Leukemia Research. 2019; 83 ():106171.

Chicago/Turabian Style

Dipenkumar Modi; Malini Surapaneni; Seongho Kim; Lois Ayash; Asif Alavi; Voravit Ratanatharathorn; Abhinav Deol; Joseph P. Uberti. 2019. "Allogeneic stem cell transplant provides durable response in peripheral T-cell lymphoma." Leukemia Research 83, no. : 106171.

Study protocol
Published: 02 December 2017 in BMC Cancer
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Cancer clinical trials are essential for testing new treatments and represent state-of-the-art cancer treatment, but only a small percentage of patients ever enroll in a trial. Under-enrollment is an even greater problem among minorities, particularly African Americans, representing a racial/ethnic disparity in cancer care. One understudied cause is patient-physician communication, which is often of poor quality during clinical interactions between African-American patients and non-African-American physicians. Partnering Around Cancer Clinical Trials (PACCT) involves a transdisciplinary theoretical model proposing that patient and physician individual attitudes and beliefs and their interpersonal communication during racially discordant clinical interactions influence outcomes related to patients’ decisions to participate in a trial. The overall goal of the study is to test a multilevel intervention designed to increase rates at which African-American and White men with prostate cancer make an informed decision to participate in a clinical trial. Data collection will occur at two NCI-designated comprehensive cancer centers. Participants include physicians who treat men with prostate cancer and their African-American and White patients who are potentially eligible for a clinical trial. The study uses two distinct research designs to evaluate the effects of two behavioral interventions, one focused on patients and the other on physicians. The primary goal is to increase the number of patients who decide to enroll in a trial; secondary goals include increasing rates of physician trial offers, improving the quality of patient-physician communication during video recorded clinical interactions in which trials may be discussed, improving patients’ understanding of trials offered, and increasing the number of patients who actually enroll. Aims are to 1) determine the independent and combined effects of the two interventions on outcomes; 2) compare the effects of the interventions on African-American versus White men; and 3) examine the extent to which patient-physician communication mediates the effect of the interventions on the outcomes. PACCT has the potential to identify ways to increase clinical trial rates in a diverse patient population. The research can also improve access to high quality clinical care for African American men bearing the disproportionate burden of disparities in prostate and other cancers. Clinical Trials.gov registration number: NCT02906241 (September 8, 2016).

ACS Style

Susan Eggly; Lauren M. Hamel; Elisabeth Heath; Mark A. Manning; Terrance L. Albrecht; Ellen Barton; Mark Wojda; Tanina Foster; Michael Carducci; Dina Lansey; Ting Wang; Rehab Abdallah; Narineh Abrahamian; Seongho Kim; Nicole Senft; Louis A. Penner. Partnering around cancer clinical trials (PACCT): study protocol for a randomized trial of a patient and physician communication intervention to increase minority accrual to prostate cancer clinical trials. BMC Cancer 2017, 17, 1 -12.

AMA Style

Susan Eggly, Lauren M. Hamel, Elisabeth Heath, Mark A. Manning, Terrance L. Albrecht, Ellen Barton, Mark Wojda, Tanina Foster, Michael Carducci, Dina Lansey, Ting Wang, Rehab Abdallah, Narineh Abrahamian, Seongho Kim, Nicole Senft, Louis A. Penner. Partnering around cancer clinical trials (PACCT): study protocol for a randomized trial of a patient and physician communication intervention to increase minority accrual to prostate cancer clinical trials. BMC Cancer. 2017; 17 (1):1-12.

Chicago/Turabian Style

Susan Eggly; Lauren M. Hamel; Elisabeth Heath; Mark A. Manning; Terrance L. Albrecht; Ellen Barton; Mark Wojda; Tanina Foster; Michael Carducci; Dina Lansey; Ting Wang; Rehab Abdallah; Narineh Abrahamian; Seongho Kim; Nicole Senft; Louis A. Penner. 2017. "Partnering around cancer clinical trials (PACCT): study protocol for a randomized trial of a patient and physician communication intervention to increase minority accrual to prostate cancer clinical trials." BMC Cancer 17, no. 1: 1-12.

Journal article
Published: 17 October 2017 in Journal for ImmunoTherapy of Cancer
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Background There is an unmet need to determine factors predictive of clinical benefit, to guide therapeutic sequencing and selection in metastatic RCC (mRCC). We evaluated clinical factors such as the neutrophil lymphocyte ratio (NLR) and duration of prior anti-vascular endothelial growth factor (VEGF) inhibitors, as predictors of response rate, progression free survival (PFS) and overall survival (OS) in mRCC patients treated with immune checkpoint inhibitor (ICI). Methods Regulatory approval was obtained. A single center retrospective chart review of mRCC patients at Karmanos Cancer Institute, treated with ICI based therapy (PD-1/PD-L1 inhibitors) was conducted. Data were collected on demographics, smoking status, prognostic scoring (Memorial Sloan Kettering and Heng criteria), NLR pretherapy, post 1 and 4 doses of ICI, and duration of prior anti-VEGF therapy ≥6 months or <6. Results 42 patients were evaluated with median age of 61 years (range, 24-85). Pretherapy NLR < 3 and ≥3 was seen in 19 (45%) and 23 (55%) patients, respectively. 24 (57%) and 18 (43%) patients had prior anti-VEGF inhibitors for a duration of ≥6 months and <6 months, respectively. 12 (29%), 22 (52%) and 8 (19%) patients had favorable, intermediate and poor risk disease based on Heng criteria, respectively. Multivariable analysis showed pretherapy NLR ≥3 was predictive of shorter PFS and OS when treated with ICI with median 3.08 months and 13.50 months, respectively, versus 15.57 months and not reached for NLR < 3 (adjusted p-values =0.003 and 0.025, respectively). Prior anti-VEGF therapy <6 months was predictive of increased likelihood of benefit from ICI therapies (adjusted p = 0.028). The median PFS was 3.72 months and 14.33 months, respectively, in cases with prior anti-VEGF therapy for ≥6 months and <6 months. Conclusion Pretherapy NLR <3 and duration of prior anti-VEGF therapy of <6 months, are independent statistically significant predictors of longer PFS and OS with ICI therapy in mRCC. Validation is required in a larger sample size with multi-institutional collaboration.

ACS Style

Ghayathri Jeyakumar; Seongho Kim; Naresh Bumma; Craig Landry; Cynthia Silski; Stacey Suisham; Brenda Dickow; Elisabeth Heath; Joseph Fontana; Ulka Vaishampayan. Neutrophil lymphocyte ratio and duration of prior anti-angiogenic therapy as biomarkers in metastatic RCC receiving immune checkpoint inhibitor therapy. Journal for ImmunoTherapy of Cancer 2017, 5, 82 -82.

AMA Style

Ghayathri Jeyakumar, Seongho Kim, Naresh Bumma, Craig Landry, Cynthia Silski, Stacey Suisham, Brenda Dickow, Elisabeth Heath, Joseph Fontana, Ulka Vaishampayan. Neutrophil lymphocyte ratio and duration of prior anti-angiogenic therapy as biomarkers in metastatic RCC receiving immune checkpoint inhibitor therapy. Journal for ImmunoTherapy of Cancer. 2017; 5 (1):82-82.

Chicago/Turabian Style

Ghayathri Jeyakumar; Seongho Kim; Naresh Bumma; Craig Landry; Cynthia Silski; Stacey Suisham; Brenda Dickow; Elisabeth Heath; Joseph Fontana; Ulka Vaishampayan. 2017. "Neutrophil lymphocyte ratio and duration of prior anti-angiogenic therapy as biomarkers in metastatic RCC receiving immune checkpoint inhibitor therapy." Journal for ImmunoTherapy of Cancer 5, no. 1: 82-82.

Original article
Published: 02 April 2017 in Supportive Care in Cancer
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Although fluoroquinolone prophylaxis is frequently utilized in autologous hematopoietic stem cell transplant (AHSCT) patients, its impact on morbidity and mortality is uncertain. This study investigates the role of quinolone prophylaxis after AHSCT in recent years. We conducted a retrospective review of 291 consecutive adult patients who underwent AHSCT for malignant disorders, between June 2013 and January 2015. Outcomes were compared between patients who received norfloxacin prophylaxis and those who did not. The endpoints were mortality during prophylaxis and at 100 days after transplant, frequency of ICU admissions, and incidence and type of bacteremia. Of 291 patients, 252 patients received norfloxacin prophylaxis and 39 patients did not. The mortality during prophylaxis and at 100 days as well as the median number of days of hospitalization following AHSCT did not differ between the two groups. No differences were noted in the frequency of ICU admission, incidence of septic shock, and duration of ICU stay. Patients who did not receive prophylaxis had a significantly higher rate of neutropenic fever (97%) than patients who received prophylaxis (77%) (p = 0.005). The patients with prophylaxis demonstrated a significantly higher rate of gram-positive bacteremia as compared to those without prophylaxis (p = 0.002). Frequency of Clostridium difficile infection was similar during and post-prophylaxis. More antibiotic use was noted among patients without prophylaxis [97%; median 9 (range, 5–24) days] compared to patients with prophylaxis [79%; median 7 (range, 3–36) days, p = 0.04]. Although fluoroquinolone prophylaxis reduced the incidence of neutropenic fever and antibiotic use in AHSCT, it did not alter mortality or morbidity.

ACS Style

Dipenkumar Modi; Hyejeong Jang; Seongho Kim; Malini Surapaneni; Kamya Sankar; Abhinav Deol; Lois Ayash; Divaya Bhutani; Lawrence G. Lum; Voravit Ratanatharathorn; Richard Manasa; Kendra Mellert; Pranatharthi Chandrasekar; Joseph P. Uberti. Fluoroquinolone prophylaxis in autologous hematopoietic stem cell transplant recipients. Supportive Care in Cancer 2017, 25, 2593 -2601.

AMA Style

Dipenkumar Modi, Hyejeong Jang, Seongho Kim, Malini Surapaneni, Kamya Sankar, Abhinav Deol, Lois Ayash, Divaya Bhutani, Lawrence G. Lum, Voravit Ratanatharathorn, Richard Manasa, Kendra Mellert, Pranatharthi Chandrasekar, Joseph P. Uberti. Fluoroquinolone prophylaxis in autologous hematopoietic stem cell transplant recipients. Supportive Care in Cancer. 2017; 25 (8):2593-2601.

Chicago/Turabian Style

Dipenkumar Modi; Hyejeong Jang; Seongho Kim; Malini Surapaneni; Kamya Sankar; Abhinav Deol; Lois Ayash; Divaya Bhutani; Lawrence G. Lum; Voravit Ratanatharathorn; Richard Manasa; Kendra Mellert; Pranatharthi Chandrasekar; Joseph P. Uberti. 2017. "Fluoroquinolone prophylaxis in autologous hematopoietic stem cell transplant recipients." Supportive Care in Cancer 25, no. 8: 2593-2601.

Journal article
Published: 03 November 2016 in Molecular Cancer
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The CXCL12/CXCR4 axis transactivates HER2 and promotes intraosseous tumor growth. To further explore the transactivation of HER2 by CXCL12, we investigated the role of small GTP protein Gαi2 in Src and HER2 phosphorylation in lipid raft membrane microdomains and the significance of CXCR4 in prostate cancer bone tumor growth. We used a variety of methods such as lipid raft isolation, invasion assays, an in vivo model of intratibial tumor growth, bone histomorphometry, and immunohistochemistry to determine the role of CXCR4 signaling in lipid raft membrane microdomains and effects of targeting of CXCR4 for bone tumor growth. We determined that (a) CXCL12/CXCR4 transactivation of EGFR and HER2 is confined to lipid raft membrane microdomains, (b) CXCL12 activation of HER2 and Src is mediated by small GTP proteins in lipid rafts, (c) inhibition of the CXCL12/CXCR4 axis through plerixafor abrogates the initial establishment of tumor growth without affecting the growth of established bone tumors, and (d) inhibition of EGFR signaling through gefitinib leads to inhibition of established bone tumor growth. These data suggest that lipid raft membrane microdomains are key sites for CXCL12/CXCR4 transactivation of HER2 via small GTP binding protein Gαi2 and Src kinase. The initial establishment of prostate cancer is supported by the endosteal niche, and blocking the CXCL12/CXCR4 axis of this niche along with its downstream signaling severely compromises initial establishment of tumors in the bone microenvironment, whereas expanding bone tumors are sensitive only to the members of growth factor receptor inhibition.

ACS Style

M. Katie Conley-LaComb; Louie Semaan; Rajareddy Singareddy; Yanfeng Li; Elisabeth I. Heath; Seongho Kim; Michael L. Cher; Sreenivasa R. Chinni. Pharmacological targeting of CXCL12/CXCR4 signaling in prostate cancer bone metastasis. Molecular Cancer 2016, 15, 1 -13.

AMA Style

M. Katie Conley-LaComb, Louie Semaan, Rajareddy Singareddy, Yanfeng Li, Elisabeth I. Heath, Seongho Kim, Michael L. Cher, Sreenivasa R. Chinni. Pharmacological targeting of CXCL12/CXCR4 signaling in prostate cancer bone metastasis. Molecular Cancer. 2016; 15 (1):1-13.

Chicago/Turabian Style

M. Katie Conley-LaComb; Louie Semaan; Rajareddy Singareddy; Yanfeng Li; Elisabeth I. Heath; Seongho Kim; Michael L. Cher; Sreenivasa R. Chinni. 2016. "Pharmacological targeting of CXCL12/CXCR4 signaling in prostate cancer bone metastasis." Molecular Cancer 15, no. 1: 1-13.

Validation study
Published: 22 September 2016 in Computer Methods and Programs in Biomedicine
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Stable isotope labeling by amino acids in cell culture (SILAC) is a practical and powerful approach for quantitative proteomic analysis. A key advantage of SILAC is the ability to simultaneously detect the isotopically labeled peptides in a single instrument run and so guarantee relative quantitation for a large number of peptides without introducing any variation caused by separate experiment. However, there are a few approaches available to assessing protein ratios and none of the existing algorithms pays considerable attention to the proteins having only one peptide hit. We introduce new quantitative approaches to dealing with SILAC protein-level summary using classification-based methodologies, such as Gaussian mixture models with EM algorithms and its Bayesian approach as well as K-means clustering. In addition, a new approach is developed using Gaussian mixture model and a stochastic, metaheuristic global optimization algorithm, particle swarm optimization (PSO), to avoid either a premature convergence or being stuck in a local optimum. Our simulation studies show that the newly developed PSO-based method performs the best among others in terms of F1 score and the proposed methods further demonstrate the ability of detecting potential markers through real SILAC experimental data. No matter how many peptide hits the protein has, the developed approach can be applicable, rescuing many proteins doomed to removal. Furthermore, no additional correction for multiple comparisons is necessary for the developed methods, enabling direct interpretation of the analysis outcomes.

ACS Style

Seongho Kim; Nicholas Carruthers; Joohyoung Lee; Sreenivasa Chinni; Paul Stemmer. Classification-based quantitative analysis of stable isotope labeling by amino acids in cell culture (SILAC) data. Computer Methods and Programs in Biomedicine 2016, 137, 137 -148.

AMA Style

Seongho Kim, Nicholas Carruthers, Joohyoung Lee, Sreenivasa Chinni, Paul Stemmer. Classification-based quantitative analysis of stable isotope labeling by amino acids in cell culture (SILAC) data. Computer Methods and Programs in Biomedicine. 2016; 137 ():137-148.

Chicago/Turabian Style

Seongho Kim; Nicholas Carruthers; Joohyoung Lee; Sreenivasa Chinni; Paul Stemmer. 2016. "Classification-based quantitative analysis of stable isotope labeling by amino acids in cell culture (SILAC) data." Computer Methods and Programs in Biomedicine 137, no. : 137-148.

Journal article
Published: 03 August 2016 in Computational Statistics & Data Analysis
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Compared to other analytical platforms, comprehensive two-dimensional gas chromatography coupled with mass spectrometry (GC×GC–MS) has much increased separation power for analysis of complex samples and thus is increasingly used in metabolomics for biomarker discovery. However, accurate peak detection remains a bottleneck for wide applications of GC×GC–MS. Therefore, the normal–exponential–Bernoulli (NEB) model is generalized by gamma distribution and a new peak detection algorithm using the Normal–Gamma–Bernoulli (NGB) model is developed. Unlike the NEB model, the NGB model has no closed-form analytical solution, hampering its practical use in peak detection. To circumvent this difficulty, three numerical approaches, which are fast Fourier transform (FFT), the first-order and the second-order delta methods (D1 and D2), are introduced. The applications to simulated data and two real GC×GC–MS data sets show that the NGB-D1 method performs the best in terms of both computational expense and peak detection performance.

ACS Style

Seongho Kim; Hyejeong Jang; Imhoi Koo; Joohyoung Lee; Xiang Zhang. Normal–Gamma–Bernoulli peak detection for analysis of comprehensive two-dimensional gas chromatography mass spectrometry data. Computational Statistics & Data Analysis 2016, 105, 96 -111.

AMA Style

Seongho Kim, Hyejeong Jang, Imhoi Koo, Joohyoung Lee, Xiang Zhang. Normal–Gamma–Bernoulli peak detection for analysis of comprehensive two-dimensional gas chromatography mass spectrometry data. Computational Statistics & Data Analysis. 2016; 105 ():96-111.

Chicago/Turabian Style

Seongho Kim; Hyejeong Jang; Imhoi Koo; Joohyoung Lee; Xiang Zhang. 2016. "Normal–Gamma–Bernoulli peak detection for analysis of comprehensive two-dimensional gas chromatography mass spectrometry data." Computational Statistics & Data Analysis 105, no. : 96-111.

Research article
Published: 19 August 2014 in Journal of Chemometrics
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Compound identification is a critical process in metabolomics. The widely used approach for compound identification in gas chromatography–mass spectrometry‐based metabolomics is spectrum matching, in which the mass spectral similarity between an experimental mass spectrum and each mass spectrum in a reference library is calculated. While various similarity measures have been developed to improve the overall accuracy of compound identification, little attention has been paid to reducing the false discovery rate. We, therefore, develop an approach for controlling the false identification rate using the distribution of the difference between the first and second highest spectral similarity scores. We further propose a model‐based approach to achieving a desired true positive rate. The developed method is applied to the National Institute of Standards and Technology mass spectral library, and its performance is compared with that of the conventional approach that uses only the maximum spectral similarity score. The results show that the developed method achieves a significantly higher F1 score and positive predictive value than did the conventional approach. Copyright © 2014 John Wiley & Sons, Ltd.

ACS Style

Seongho Kim; Xiang Zhang. Discovery of false identification using similarity difference in GC-MS-based metabolomics. Journal of Chemometrics 2014, 29, 80 -86.

AMA Style

Seongho Kim, Xiang Zhang. Discovery of false identification using similarity difference in GC-MS-based metabolomics. Journal of Chemometrics. 2014; 29 (2):80-86.

Chicago/Turabian Style

Seongho Kim; Xiang Zhang. 2014. "Discovery of false identification using similarity difference in GC-MS-based metabolomics." Journal of Chemometrics 29, no. 2: 80-86.

Journal article
Published: 09 July 2014 in Chemometrics and Intelligent Laboratory Systems
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The goal of metabolic association networks is to identify topology of a metabolic network for a better understanding of molecular mechanisms. An accurate metabolic association network enables investigation of the functional behavior of metabolites in a cell or tissue. Gaussian Graphical model (GGM)-based methods have been widely used in genomics to infer biological networks. However, the performance of various GGM-based methods for the construction of metabolic association networks remains unknown in metabolomics. The performance of principal component regression (PCR), independent component regression (ICR), shrinkage covariance estimate (SCE), partial least squares regression (PLSR), and extrinsic similarity (ES) methods in constructing metabolic association networks was compared by estimating partial correlation coefficient matrices when the number of variables is larger than the sample size. To do this, the sample size and the network density (complexity) were considered as variables for network construction. Simulation studies show that PCR and ICR are more stable to the sample size and the network density than SCE and PLSR in terms of F1 scores. These methods were further applied to the analysis of experimental metabolomics data acquired from metabolite extract of mouse liver. For the simulated data, the proposed methods PCR and ICR outperform other methods when the network density is large, while PLSR and SCE perform better when the network density is small. As for the experimental metabolomics data, PCR and ICR discover more significant edges and perform better than PLSR and SCE when the discovered edges are evaluated using KEGG pathway. These results suggest that the metabolic network might be more complex and therefore, PCR and ICR have the advantage over PLSR and SCE in constructing the metabolic association networks.

ACS Style

Imhoi Koo; Xiaoli Wei; Xue Shi; Zhanxiang Zhou; Seongho Kim; Xiang Zhang. Constructing metabolic association networks using high-dimensional mass spectrometry data. Chemometrics and Intelligent Laboratory Systems 2014, 138, 193 -202.

AMA Style

Imhoi Koo, Xiaoli Wei, Xue Shi, Zhanxiang Zhou, Seongho Kim, Xiang Zhang. Constructing metabolic association networks using high-dimensional mass spectrometry data. Chemometrics and Intelligent Laboratory Systems. 2014; 138 ():193-202.

Chicago/Turabian Style

Imhoi Koo; Xiaoli Wei; Xue Shi; Zhanxiang Zhou; Seongho Kim; Xiang Zhang. 2014. "Constructing metabolic association networks using high-dimensional mass spectrometry data." Chemometrics and Intelligent Laboratory Systems 138, no. : 193-202.

Journal article
Published: 22 October 2013 in Computer Methods and Programs in Biomedicine
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The statistical identifiability of nonlinear pharmacokinetic (PK) models with the Michaelis-Menten (MM) kinetic equation is considered using a global optimization approach, which is particle swarm optimization (PSO). If a model is statistically non-identifiable, the conventional derivative-based estimation approach is often terminated earlier without converging, due to the singularity. To circumvent this difficulty, we develop a derivative-free global optimization algorithm by combining PSO with a derivative-free local optimization algorithm to improve the rate of convergence of PSO. We further propose an efficient approach to not only checking the convergence of estimation but also detecting the identifiability of nonlinear PK models. PK simulation studies demonstrate that the convergence and identifiability of the PK model can be detected efficiently through the proposed approach. The proposed approach is then applied to clinical PK data along with a two-compartmental model.

ACS Style

Seongho Kim; Lang Li. Statistical identifiability and convergence evaluation for nonlinear pharmacokinetic models with particle swarm optimization. Computer Methods and Programs in Biomedicine 2013, 113, 413 -32.

AMA Style

Seongho Kim, Lang Li. Statistical identifiability and convergence evaluation for nonlinear pharmacokinetic models with particle swarm optimization. Computer Methods and Programs in Biomedicine. 2013; 113 (2):413-32.

Chicago/Turabian Style

Seongho Kim; Lang Li. 2013. "Statistical identifiability and convergence evaluation for nonlinear pharmacokinetic models with particle swarm optimization." Computer Methods and Programs in Biomedicine 113, no. 2: 413-32.

Research article
Published: 04 November 2012 in Statistical Methods in Medical Research
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The probability model for periodic screening was extended to provide statistical inference for sensitivity depending on sojourn time, in which the sensitivity was modeled as a function of time spent in the preclinical state and the sojourn time. The likelihood function with the proposed sensitivity model was then evaluated with simulated data to check its reliability in terms of the mean estimation and the standard error. Simulation results showed that the maximum likelihood estimates of the proposed model have little bias and small standard errors. The extended probability model was further applied to the Johns Hopkins Lung Project data using both maximum likelihood estimation and Bayesian Markov chain Monte Carlo.

ACS Style

Seongho Kim; Dongfeng Wu. Estimation of sensitivity depending on sojourn time and time spent in preclinical state. Statistical Methods in Medical Research 2012, 25, 728 -740.

AMA Style

Seongho Kim, Dongfeng Wu. Estimation of sensitivity depending on sojourn time and time spent in preclinical state. Statistical Methods in Medical Research. 2012; 25 (2):728-740.

Chicago/Turabian Style

Seongho Kim; Dongfeng Wu. 2012. "Estimation of sensitivity depending on sojourn time and time spent in preclinical state." Statistical Methods in Medical Research 25, no. 2: 728-740.