Pegteograstim prophylaxis for chemotherapy-induced neutropenia and febrile neutropenia: a prospective, observational, postmarketing surveillance study in Korea.

PURPOSE: This observational study aimed to evaluate the safety and efficacy of pegteograstim prophylaxis in patients with lymphoma and solid malignancies. METHODS: This study was conducted at 18 sites in Korea between November 2015 and August 2018. RESULTS: In total, 611 patients (female, 61.2%) with a median age of 58 (range, 18-88) years were included. Most patients had lymphomas (n = 371, 60.7%) and breast cancer (n = 230, 37.6%) and were administered R-CHOP21 (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone per 21 days) (n = 284, 46.5%) and AC (doxorubicin and cyclophosphamide) (n = 177, 29.0%). The total pegteograstim dose in the 611 patients was 14,970 mg (2495 doses), with each patient receiving an average daily dose of 6.0 mg. Neutropenia grade 4 occurred in 97 patients (15.9%), and febrile neutropenia (FN) occurred in 31 patients (5.1%). Among the 611 patients, 267 patients (43.7%) developed 882 adverse events (AEs), and 11 patients (1.8%) experienced 18 adverse drug reactions (ADRs). There were 62 patients (10.2%) who experienced 81 cases of serious adverse events (SAEs), with FN and pneumonia being the most frequent at 14 and 13 episodes, respectively, in 13 patients (2.1%). Meanwhile, 1 patient (0.2%) developed 2 episodes of serious ADRs (grade 1 and grade 2 hypotension). No safety concerns in the elderly and patients with liver and/or renal disease were identified. CONCLUSION: The prophylactic use of pegteograstim might have good overall safety and efficacy in patients with lymphomas and solid malignancies in routine clinical practice, even in those who are elderly and have liver and renal diseases.

Directed evolution of the 3-hydroxypropionic acid production pathway by engineering aldehyde dehydrogenase using a synthetic selection device.

3-Hydroxypropionic acid (3-HP) is an important platform chemical, and biological production of 3-HP from glycerol as a carbon source using glycerol dehydratase (GDHt) and aldehyde dehydrogenase (ALDH) has been revealed to be effective because it involves a relatively simple metabolic pathway and exhibits higher yield and productivity than other biosynthetic pathways. Despite the successful attempts of 3-HP production from glycerol, the biological process suffers from problems arising from low activity and inactivation of the two enzymes. To apply the directed evolutionary approach to engineer the 3-HP production system, we constructed a synthetic selection device using a 3-HP-responsive transcription factor and developed a selection approach for screening 3-HP-producing microorganisms. The method was applied to an ALDH library, specifically aldehyde-binding site library of alpha-ketoglutaric semialdehyde dehydrogenase (KGSADH). Only two serial cultures resulted in enrichment of strains showing increased 3-HP production, and an isolated KGSADH variant enzyme exhibited a 2.79-fold higher catalytic efficiency toward its aldehyde substrate than the wild-type one. This approach will provide the simple and efficient tool to engineer the pathway enzymes in metabolic engineering.

Improving the quality of life in a breast cancer patient and caregiver: Protocol for the application of the integrative medical service model.

BACKGROUND: Patients with chronic diseases require ongoing treatment, and caregivers face financial burdens as well as psychological and physical difficulties. However, the current healthcare system does not provide adequate systems or services to address the difficulties that patients and caregivers face. PURPOSE: The purpose of this study was to conduct an observational case study in order to evaluate and improve the application of an integrative healthcare service model developed for distress management and improved quality of life in breast cancer (BC) patients and caregivers. METHOD: The integrative healthcare service model was intensively applied to a patient-caregiver pair in this observational study. This was followed by gathering feedback from participants and experts, as well as reflecting on the content of the feedback in order to improve the model further. RESULTS: This study will then modify and improve the program with feedback and provide integrative medical services to a BC patient and caregiver. CONCLUSION: This study used the BC patients' pain management and quality of life enhancement model, aiming to provide basic data for the establishment of a healthcare service system for patients suffering from chronic pain due to diseases such as BC by systematically integrating previously applied interventions into the current healthcare system and soliciting feedback from patients and caregivers.

Perioperative clinical outcomes after robotic thyroidectomy for thyroid carcinoma: a multicenter study.

OBJECTIVES: Robotic thyroidectomy and lymph node dissection is rapidly emerging as an alternative to conventional endoscopic thyroidectomy for thyroid carcinoma. Robot techniques incorporate the advantages of endoscopic procedures while overcoming some of the problems. We present the largest multi-institution clinical study of robotic thyroidectomy for thyroid carcinomas. The robotic thyroidectomy involved gasless transaxillary approach using the da Vinci surgical robot system. METHODS: We reviewed a database of 1,043 consecutive patients with low-risk differentiated thyroid carcinoma who underwent robotic thyroidectomy between October 2007 and August 2009. Operations were performed by five surgeons at four academic centers. We analyzed perioperative, clinical, and pathological data. RESULTS: The study involved 71 men and 972 women, with a mean age of 39 (range, 15-70) years. All operations were performed successfully without any need for conventional open or endoscopic conversion. There were 366 total thyroidectomies and 677 subtotal thyroidectomies with cervical lymph node dissection. The mean overall operation time and console time were 132.4 and 63.9 min, respectively. There were ten (1%) major postoperative morbidities. The mean tumor size was 0.8 (range, 0.1-6.0) cm, and the mean number of retrieved central lymph nodes was 5.1 ± 3.8 (range, 0-26). The mean postoperative hospital stay was 2.9 (range, 1-8) days. CONCLUSIONS: Robotic thyroidectomy using gasless transaxillary method was feasible, safe, and provided good outcomes for patients with differentiated thyroid carcinoma. Robotic technology overcame some technical limitations associated with conventional endoscopy.

KAI1/CD82 decreases Rac1 expression and cell proliferation through PI3K/Akt/mTOR pathway in H1299 lung carcinoma cells.

Although the KAI1/CD82 protein has been reported to inhibit cell metastasis in many studies, its mechanism of action has not yet been fully elucidated. In the present study, we investigated the possible effects of KAI1/CD82 on the metastatic phenotype in H1299 lung carcinoma cells. These studies were based on the pivotal role that the acquisition of motile phenotype plays on the initial steps of metastasis. KAI1/CD82-mediated morphological changes were observed using phase contrast microscopy. We report here, that a KAI1/CD82-induced phenotypic change was involved in the decrease of Rac1 expression and GTPase activity. However, we found that KAI1/CD82 did not regulate Rac1 mRNA levels. This suggests the existence of another regulatory mechanism of Rac1 protein maturation or activation. To identify the signaling pathway of Rac1 regulation, we investigated the PI3K/Akt/mTOR pathway, since the PI3K/Akt pathway regulates Rac1 activation and mTOR is known to play a regulatory role in protein translation. H1299/CD82-transfectants showed lower mTOR expression and cell growth than the control group. The data obtained from this study suggested that KAI1/CD82 decreased the metastatic phenotype of H1299 lung carcinoma cells by down-regulating Rac1 expression through the PI3K/Akt/mTOR pathway.

Engineering an aldehyde dehydrogenase toward its substrates, 3-hydroxypropanal and NAD+, for enhancing the production of 3-hydroxypropionic acid.

3-Hydroxypropionic acid (3-HP) can be produced via the biological route involving two enzymatic reactions: dehydration of glycerol to 3-hydroxypropanal (3-HPA) and then oxidation to 3-HP. However, commercial production of 3-HP using recombinant microorganisms has been hampered with several problems, some of which are associated with the toxicity of 3-HPA and the efficiency of NAD+ regeneration. We engineered α-ketoglutaric semialdehyde dehydrogenase (KGSADH) from Azospirillum brasilense for the second reaction to address these issues. The residues in the binding sites for the substrates, 3-HPA and NAD+, were randomized, and the resulting libraries were screened for higher activity. Isolated KGSADH variants had significantly lower Km values for both the substrates. The enzymes also showed higher substrate specificities for aldehyde and NAD+, less inhibition by NADH, and greater resistance to inactivation by 3-HPA than the wild-type enzyme. A recombinant Pseudomonas denitrificans strain with one of the engineered KGSADH variants exhibited less accumulation of 3-HPA, decreased levels of inactivation of the enzymes, and higher cell growth than that with the wild-type KGSADH. The flask culture of the P. denitrificans strain with the mutant KGSADH resulted in about 40% increase of 3-HP titer (53 mM) compared with that using the wild-type enzyme (37 mM).

Robotic versus Endoscopic Thyroidectomy for Thyroid Cancers: A Multi-Institutional Analysis of Early Postoperative Outcomes and Surgical Learning Curves.

Robotic thyroidectomy is an emerging technique with postoperative outcomes that are at least comparable to those of conventional endoscopic thyroidectomy, with some end-points appearing superior. Our multicenter series represents the largest comparison of robotic and endoscopic thyroidectomy to date, with results suggesting a comparable robot technology we used that could overcome some of the technical limitations associated with conventional endoscopic procedures, with reduced operation times and increased lymph node retrieval. Moreover, we found that the learning curve for robotic thyroidectomy was shorter than that for endoscopic thyroidectomy.