In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

Due to an oversight of the editorial team, the original version of this article contained an error in the list of authors.

We investigated whether betulin affects the gene expression, secretion and proteolytic activity of matrix metalloproteinase-3 (MMP-3) in primary cultured rabbit articular chondrocytes, as well as in vivo production of MMP-3 in the rat knee joint to evaluate the potential chondroprotective effect of betulin. Rabbit articular chondrocytes were cultured and reverse transcription-polymerase chain reaction (RT-PCR) was used to measure interleukin-1β (IL-1β)-induced gene expression of MMP-3, MMP-1, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4), ADAMTS-5 and type II collagen. Effect of betulin on IL-1β-induced secretion and proteolytic activity of MMP-3 was investigated using western blot analysis and casein zymography, respectively. Effect of betulin on MMP-3 protein production was also examined in vivo. The results were as follows: (1) betulin inhibited the gene expression of MMP-3, MMP-1, MMP-13, ADAMTS-4, and ADAMTS-5, but increased the gene expression of type II collagen; (2) betulin inhibited the secretion and proteolytic activity of MMP-3; (3) betulin suppressed the production of MMP-3 protein in vivo. These results suggest that betulin can regulate the gene expression, secretion, and proteolytic activity of MMP-3, by directly acting on articular chondrocytes.
Animals ; Blotting, Western ; Caseins ; Chondrocytes* ; Collagen Type II ; Gene Expression* ; Knee Joint* ; Knee* ; Osteoarthritis ; Rats* ; Thrombospondins

Relapsing polychondritis is an uncommon disease associated with inflammation in cartilaginous tissues throughout the body, particularly affecting the cartilaginous structures of ears, nose, joints, and respiratory tract. Several autoimmune diseases, including vasculitis, are associated with the concurrent relapsing polychondritis. However, ankylosing spondylitis primarily affecting the sacroiliac joints and spine is rare in patients with relapsing polychondritis. We report on a 54-year-old man with concurrently relapsing polychondritis and ankylosing spondylitis.
Autoimmune Diseases ; Ear ; Humans ; Inflammation ; Joints ; Middle Aged ; Nose ; Polychondritis, Relapsing* ; Respiratory System ; Sacroiliac Joint ; Spine ; Spondylitis, Ankylosing* ; Vasculitis

We evaluated the chondroprotective effects of wogonin by investigating its effects on the gene expression and production of matrix metalloproteinase-3 (MMP-3) in primary cultured rabbit articular chondrocytes, as well as on production of MMP-3 in the rat knee. Rabbit articular chondrocytes were cultured in a monolayer, and RT-PCR was used to measure interleukin-1beta (IL-1beta)-induced expression of MMP-3, MMP-1, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4), and type II collagen. In rabbit articular chondrocytes, the effects of wogonin on IL-1beta-induced production and proteolytic activity of MMP-3 were investigated using western blot analysis and casein zymography, respectively. The effect of wogonin on MMP-3 protein production was also examined in vivo. In rabbit articular chondrocytes, wogonin inhibited the expression of MMP-3, MMP-1, MMP-13, and ADAMTS-4, but increased expression of type II collagen. Furthermore, wogonin inhibited the production and proteolytic activity of MMP-3 in vitro, and inhibited production of MMP-3 protein in vivo. These results suggest that wogonin can regulate the gene expression and production of MMP-3, by directly acting on articular chondrocytes.
Animals ; Blotting, Western ; Caseins ; Chondrocytes ; Collagen Type II ; Gene Expression ; Interleukin-1beta ; Knee ; Models, Theoretical* ; Osteoarthritis* ; Rats ; Thrombospondins

IgG4-related sclerosing disease is a disease entity that has recently attracted attention, manifesting as a multiorgan disease characterized by high serum IgG4 levels, extensive IgG4-positive plasma cells and lymphocyte infiltration of the affected organs, with the pancreas (autoimmune pancreatitis) and kidney as representative targets. In cases of renal involvement, parenchymal lesions are predominant, such as renal cortical lesions or diffuse renal enlargement. However, mass-like lesions involving the renal pelvis are very rare, and mass forming or pelvic involvement types should be distinguished from lymphomas, metastatic cancers and other genitourinary malignancies to avoid unnecessary surgery. Herein, we report a case of IgG4-related sclerosing disease involving the kidney as an unusual involvement pattern presenting as a mass-like lesion with pelvic and perirenal involvement.
Immunoglobulin G ; Kidney ; Kidney Diseases* ; Kidney Pelvis ; Lymphocytes ; Lymphoma ; Pancreas* ; Plasma Cells ; Unnecessary Procedures

BACKGROUND/AIMS: The bedside index of severity in acute pancreatitis (BISAP) is a new, convenient, prognostic multifactorial scoring system. As more data are needed before clinical application, we compared BISAP, the serum procalcitonin (PCT), and other multifactorial scoring systems simultaneously. METHODS: Fifty consecutive acute pancreatitis patients were enrolled prospectively. Blood samples were obtained at admission and after 48 hours and imaging studies were performed within 48 hours of admission. The BISAP score was compared with the serum PCT, Ranson's score, and the acute physiology and chronic health examination (APACHE)-II, Glasgow, and Balthazar computed tomography severity index (BCTSI) scores. Acute pancreatitis was graded using the Atlanta criteria. The predictive accuracy of the scoring systems was measured using the area under the receiver-operating curve (AUC). RESULTS: The accuracy of BISAP (> or = 2) at predicting severe acute pancreatitis was 84% and was superior to the serum PCT (> or = 3.29 ng/mL, 76%) which was similar to the APACHE-II score. The best cutoff value of BISAP was 2 (AUC, 0.873; 95% confidence interval, 0.770 to 0.976; p < 0.001). In logistic regression analysis, BISAP had greater statistical significance than serum PCT. CONCLUSIONS: BISAP is more accurate for predicting the severity of acute pancreatitis than the serum PCT, APACHE-II, Glasgow, and BCTSI scores.
Biological Markers/blood ; Calcitonin/*blood ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Pancreatitis/blood/*diagnosis ; Prognosis ; Prospective Studies ; Protein Precursors/*blood ; ROC Curve ; *Severity of Illness Index

Mast cells are involved in allergic responses, protection against pathogens and autoimmune diseases. Dexamethasone (Dex) and other glucocorticoids suppress FcepsilonRI-mediated release of inflammatory mediators from mast cells. The inhibition mechanisms were mainly investigated on the downstream signaling of Fc receptor activations. Here, we addressed the effects of Dex on Fc receptor expressions in rat mast cell line RBL-2H3. We measured mRNA levels of Fc receptors by real-time PCR. As expected, Dex decreased the mRNA levels of activating Fc receptor for IgE (FcepsilonR) I and increased the mRNA levels of the inhibitory Fc receptor for IgG FcgammaRIIb. Interestingly, Dex stimulated transcriptions of other activating receptors such as Fc receptors for IgG (FcgammaR) I and FcgammaRIII. To investigate the mechanisms underlying transcriptional regulation, we employed a transcription inhibitor actinomycin D and a translation inhibitor cycloheximide. The inhibition of protein synthesis without Dex treatment enhanced FcgammaRI and FcgammaRIII mRNA levels potently, while FcepsilonRI and FcgammaRIIb were minimally affected. Next, we examined expressions of the Fc receptors on cell surfaces by the flow cytometric method. Only FcgammaRIIb protein expression was significantly enhanced by Dex treatment, while FcgammaRI, FcgammaRIII and FcepsilonRI expression levels were marginally changed. Our data showed, for the first time, that Dex regulates Fc receptor expressions resulting in augmentation of the inhibitory receptor FcgammaRIIb.
Animals ; Autoimmune Diseases ; Cycloheximide ; Dactinomycin ; Dexamethasone ; Glucocorticoids ; Immunoglobulin E ; Immunoglobulin G ; Mast Cells ; Rats ; Real-Time Polymerase Chain Reaction ; Receptors, Fc ; RNA, Messenger

BACKGROUND: The aim of this study is to clarify the epidemiology of swine-origin influenza A (H1N1) virus 2009 (S-OIV) during the first month of outbreak at one of influenza clinic in Seoul, Korea. METHODS: We documented the epidemiologic and clinical features of S-OIV-confirmed cases who visited a university hospital in Northeastern Seoul between August 21 and September 20, 2009. Nasopharyngeal swab of patients with acute febrile respiratory illnesses were evaluated with rapid influenza antigen tests and multiplex RT-PCR for S-OIV and seasonal influenza A. RESULTS: A total of 5,322 patients with acute febrile respiratory illnesses were identified at our influenza clinic for the study period. S-OIV was confirmed in 309 patients by RT-PCR. The patients ranged from 2 months to 61 years of age and 189 patients (61.2%) were teenagers. Eighty-one patients had known contact with S-OIV-confirmed patients in schools (N=61), households (N=15), and healthcare facilities (N=3). Frequent symptoms were fever (94.5%), cough (73.1%), sore throat (52.1%), and rhinorrhea (50.5%). Gastrointestinal symptoms were also present in 10 patients (4.9%). Ten patients (4.9%) required hospitalizations. Seventy patients (22.7%) could not take oseltamivir at the first visits, however, all of them recovered without complication. Rapid antigen tests showed the sensitivity of 44.4% (130/294). Patients with positive antigen tests, compared with negative antigen tests, showed higher frequencies of rhinorrhea (60.8% vs 43.3%, P=0.004) and stuffy nose (33.8% vs 20.1%, P=0.012). CONCLUSION: S-OIV infections spread predominately in school-aged children during the early accelerating phase of the outbreak. Rapid influenza antigen tests were correlated with nasal discharge and obstruction.
Adolescent ; Child ; Cough ; Delivery of Health Care ; Family Characteristics ; Fever ; Hospitalization ; Humans ; Influenza A virus ; Influenza, Human ; Korea ; Nose ; Oseltamivir ; Pharyngitis ; Seasons ; Viruses