Purpose: Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS. Materials and Methods: This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches. Results: TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making. Conclusion TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

Purpose: Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS. Materials and Methods: This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches. Results: TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making. Conclusion TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

Purpose: Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS. Materials and Methods: This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches. Results: TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making. Conclusion TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

BACKGROUND: Tendinopathy is a chronic tendon disease. Mesenchymal stem cells (MSCs), known for their antiinflammatory properties, may lose effectiveness with extensive culturing. Previous research introduced ‘‘small umbilical cord–derived fast proliferating cells’’ (smumf cells), isolated using a novel minimal cube explant method. These cells maintained their MSC characteristics through long-term culture. Thus, the purpose of the present study was to assess the anti-inflammatory effects of late-passage smumf cells at P10 on tenocytes derived from degenerative rotator cuff tears in a tendinopathic environment. METHODS: The mRNA expression with respect to aging of MSCs and secretion of growth factors (GFs) by smumf cells at P10 were measured. mRNA and protein synthesis in tenocytes with respect to the tenocyte phenotype, inflammatory cytokines, and matrix- degradation enzymes were measured. The inflammatory signal pathways involving nuclear factor kappa B (NF-jB) and mitogen-activated protein kinase (MAPK) in tenocytes were also investigated. The proliferative response of degenerative tenocytes to co-culture with smumf cells over 7 days in varying IL-1β induced tendinopathic environments was investigated. RESULTS smumf cells at P10 showed no signs of aging compared to those at P3. smumf cells at P10, secreting 2,043 pg/ ml of hepatocyte growth factor (HGF), showed a 1.88-fold (p = .002) increase in HGF secretion in a tendinopathic environment. Degenerative tenocytes co-cultured with smumf cells showed significantly increased protein expression levels of collagen type I (Col I) and the Col I/III ratio by 1.46-fold (p < .001) and 1.66-fold (p < .001), respectively. The smumf cells at P10 reduced both mRNA and protein expression levels of matrix metalloproteinases-1, -2, -3, -8, -9, and -13 in tenocytes and attenuated NF-jB (phosphorylated IjBa/IjBa and phosphorylated p65/p65) and MAPK (phosphorylated p38/p38 and phosphorylated JNK/JNK) pathways activated by IL-1β. Removal of IL-1β from the co-culture accelerated the growth of tenocytes by 1.42-fold (p < .001). Removal of IL-1β accelerated tenocyte growth in co-cultures.CONCULSION Late-passage smumf cells exert anti-inflammatory effects on tenocytes derived from degenerative rotator cuff tears under a tendinopathic environment, primarily through the secretion of growth factors (GFs).

BACKGROUND: Tendinopathy is a chronic tendon disease. Mesenchymal stem cells (MSCs), known for their antiinflammatory properties, may lose effectiveness with extensive culturing. Previous research introduced ‘‘small umbilical cord–derived fast proliferating cells’’ (smumf cells), isolated using a novel minimal cube explant method. These cells maintained their MSC characteristics through long-term culture. Thus, the purpose of the present study was to assess the anti-inflammatory effects of late-passage smumf cells at P10 on tenocytes derived from degenerative rotator cuff tears in a tendinopathic environment. METHODS: The mRNA expression with respect to aging of MSCs and secretion of growth factors (GFs) by smumf cells at P10 were measured. mRNA and protein synthesis in tenocytes with respect to the tenocyte phenotype, inflammatory cytokines, and matrix- degradation enzymes were measured. The inflammatory signal pathways involving nuclear factor kappa B (NF-jB) and mitogen-activated protein kinase (MAPK) in tenocytes were also investigated. The proliferative response of degenerative tenocytes to co-culture with smumf cells over 7 days in varying IL-1β induced tendinopathic environments was investigated. RESULTS smumf cells at P10 showed no signs of aging compared to those at P3. smumf cells at P10, secreting 2,043 pg/ ml of hepatocyte growth factor (HGF), showed a 1.88-fold (p = .002) increase in HGF secretion in a tendinopathic environment. Degenerative tenocytes co-cultured with smumf cells showed significantly increased protein expression levels of collagen type I (Col I) and the Col I/III ratio by 1.46-fold (p < .001) and 1.66-fold (p < .001), respectively. The smumf cells at P10 reduced both mRNA and protein expression levels of matrix metalloproteinases-1, -2, -3, -8, -9, and -13 in tenocytes and attenuated NF-jB (phosphorylated IjBa/IjBa and phosphorylated p65/p65) and MAPK (phosphorylated p38/p38 and phosphorylated JNK/JNK) pathways activated by IL-1β. Removal of IL-1β from the co-culture accelerated the growth of tenocytes by 1.42-fold (p < .001). Removal of IL-1β accelerated tenocyte growth in co-cultures.CONCULSION Late-passage smumf cells exert anti-inflammatory effects on tenocytes derived from degenerative rotator cuff tears under a tendinopathic environment, primarily through the secretion of growth factors (GFs).

BACKGROUND: Tendinopathy is a chronic tendon disease. Mesenchymal stem cells (MSCs), known for their antiinflammatory properties, may lose effectiveness with extensive culturing. Previous research introduced ‘‘small umbilical cord–derived fast proliferating cells’’ (smumf cells), isolated using a novel minimal cube explant method. These cells maintained their MSC characteristics through long-term culture. Thus, the purpose of the present study was to assess the anti-inflammatory effects of late-passage smumf cells at P10 on tenocytes derived from degenerative rotator cuff tears in a tendinopathic environment. METHODS: The mRNA expression with respect to aging of MSCs and secretion of growth factors (GFs) by smumf cells at P10 were measured. mRNA and protein synthesis in tenocytes with respect to the tenocyte phenotype, inflammatory cytokines, and matrix- degradation enzymes were measured. The inflammatory signal pathways involving nuclear factor kappa B (NF-jB) and mitogen-activated protein kinase (MAPK) in tenocytes were also investigated. The proliferative response of degenerative tenocytes to co-culture with smumf cells over 7 days in varying IL-1β induced tendinopathic environments was investigated. RESULTS smumf cells at P10 showed no signs of aging compared to those at P3. smumf cells at P10, secreting 2,043 pg/ ml of hepatocyte growth factor (HGF), showed a 1.88-fold (p = .002) increase in HGF secretion in a tendinopathic environment. Degenerative tenocytes co-cultured with smumf cells showed significantly increased protein expression levels of collagen type I (Col I) and the Col I/III ratio by 1.46-fold (p < .001) and 1.66-fold (p < .001), respectively. The smumf cells at P10 reduced both mRNA and protein expression levels of matrix metalloproteinases-1, -2, -3, -8, -9, and -13 in tenocytes and attenuated NF-jB (phosphorylated IjBa/IjBa and phosphorylated p65/p65) and MAPK (phosphorylated p38/p38 and phosphorylated JNK/JNK) pathways activated by IL-1β. Removal of IL-1β from the co-culture accelerated the growth of tenocytes by 1.42-fold (p < .001). Removal of IL-1β accelerated tenocyte growth in co-cultures.CONCULSION Late-passage smumf cells exert anti-inflammatory effects on tenocytes derived from degenerative rotator cuff tears under a tendinopathic environment, primarily through the secretion of growth factors (GFs).

BACKGROUND: Tendinopathy is a chronic tendon disease. Mesenchymal stem cells (MSCs), known for their antiinflammatory properties, may lose effectiveness with extensive culturing. Previous research introduced ‘‘small umbilical cord–derived fast proliferating cells’’ (smumf cells), isolated using a novel minimal cube explant method. These cells maintained their MSC characteristics through long-term culture. Thus, the purpose of the present study was to assess the anti-inflammatory effects of late-passage smumf cells at P10 on tenocytes derived from degenerative rotator cuff tears in a tendinopathic environment. METHODS: The mRNA expression with respect to aging of MSCs and secretion of growth factors (GFs) by smumf cells at P10 were measured. mRNA and protein synthesis in tenocytes with respect to the tenocyte phenotype, inflammatory cytokines, and matrix- degradation enzymes were measured. The inflammatory signal pathways involving nuclear factor kappa B (NF-jB) and mitogen-activated protein kinase (MAPK) in tenocytes were also investigated. The proliferative response of degenerative tenocytes to co-culture with smumf cells over 7 days in varying IL-1β induced tendinopathic environments was investigated. RESULTS smumf cells at P10 showed no signs of aging compared to those at P3. smumf cells at P10, secreting 2,043 pg/ ml of hepatocyte growth factor (HGF), showed a 1.88-fold (p = .002) increase in HGF secretion in a tendinopathic environment. Degenerative tenocytes co-cultured with smumf cells showed significantly increased protein expression levels of collagen type I (Col I) and the Col I/III ratio by 1.46-fold (p < .001) and 1.66-fold (p < .001), respectively. The smumf cells at P10 reduced both mRNA and protein expression levels of matrix metalloproteinases-1, -2, -3, -8, -9, and -13 in tenocytes and attenuated NF-jB (phosphorylated IjBa/IjBa and phosphorylated p65/p65) and MAPK (phosphorylated p38/p38 and phosphorylated JNK/JNK) pathways activated by IL-1β. Removal of IL-1β from the co-culture accelerated the growth of tenocytes by 1.42-fold (p < .001). Removal of IL-1β accelerated tenocyte growth in co-cultures.CONCULSION Late-passage smumf cells exert anti-inflammatory effects on tenocytes derived from degenerative rotator cuff tears under a tendinopathic environment, primarily through the secretion of growth factors (GFs).