The predictive value of anticholinergic drug exposure and the outcome of pneumonia: a Danish database study.

INTRODUCTION: Older adults are susceptible to anticholinergic effects. Dysphagia and pneumonia are associated with anticholinergic usage, though a definitive causative relationship has not been established. There is no effective way to predict the prognosis of older adults with pneumonia; therefore, this study investigates the predictive value of anticholinergic burden. METHODS: Patients aged 65 years and above admitted for community-acquired pneumonia from 2011 to 2018 in Denmark were included through Danish registries. We calculated anticholinergic drug exposure using the CRIDECO Anticholinergic Load Scale (CALS). The primary outcome was in-hospital mortality, and other outcomes included intensive care unit admission, ventilator usage, length of stay, 30-day/90-day/1-year mortality, institutionalisation, home care utilisation and readmission. RESULTS: 186,735 patients were included in the in-hospital outcome analyses, 165,181 in the readmission analysis, 150,791 in the institutionalisation analysis, and 95,197 and 73,461 patients in the home care analysis at follow-up. Higher CALS score was associated with higher in-hospital mortality, with a mean risk increasing from 9.9% (CALS 0) to 16.4% (CALS >10), though the risk plateaued above a CALS score of 8. A higher CALS score was also associated with greater mortality after discharge, more home health care, more institutionalizations and higher readmission rates. CONCLUSIONS: High anticholinergic burden levels were associated with poor patient outcomes including short-/long-term mortality, dependence and readmission. It may be useful to calculate the CALS score on admission of older patients with pneumonia to predict their prognosis. This also highlights the importance of avoiding the use of drugs with a high anticholinergic burden in older patients.

Clinical practice guidelines for molecular tumor marker, 2nd edition review part 2.

In recent years, rapid advancement in gene/protein analysis technology has resulted in target molecule identification that may be useful in cancer treatment. Therefore, "Clinical Practice Guidelines for Molecular Tumor Marker, Second Edition" was published in Japan in September 2021. These guidelines were established to align the clinical usefulness of external diagnostic products with the evaluation criteria of the Pharmaceuticals and Medical Devices Agency. The guidelines were scoped for each tumor, and a clinical questionnaire was developed based on a serious clinical problem. This guideline was based on a careful review of the evidence obtained through a literature search, and recommendations were identified following the recommended grades of the Medical Information Network Distribution Services (Minds). Therefore, this guideline can be a tool for cancer treatment in clinical practice. We have already reported the review portion of "Clinical Practice Guidelines for Molecular Tumor Marker, Second Edition" as Part 1. Here, we present the English version of each part of the Clinical Practice Guidelines for Molecular Tumor Marker, Second Edition.

Referral Patterns to Speech and Language Therapy in the UK before, during, and after the COVID-19 Pandemic: Dysphagia Compared with Communication Disorders.

INTRODUCTION: Acquired swallowing impairment is a major public health issue that often leads to increased morbidity and slower recovery. Speech and language therapists (SLTs) have taken the lead in the assessment and treatment of dysphagia, which is reflected in guidelines where early intervention is recommended. This is in addition to the central role that SLTs play in the management of acquired communication impairments since research indicates that patients with communication difficulties benefit from early and intensive therapy by SLTs. This increasing demand for SLTs is expected to cause conflicting pressures in their workload and, therefore, beneficial to consider workforce planning. The aim of this study was to examine real-world data in the UK to investigate this issue regarding changes in referral patterns of patients with dysphagia and/or communication disorders to SLTs over time, to assist with workforce planning. METHODS: We interrogated the Royal College of Speech and Language Therapists Online Outcome Tool, a national database, in this retrospective cohort study. We included patients evaluated between 2018 and 2022. We performed a subgroup analysis of patients aged ≥40 years who had a primary medical diagnosis of stroke. Data on age, primary diagnosis, time on caseload, primary Therapeutic Outcome Measure (TOM) scale and initial TOM score on impairment were examined. RESULTS: From the database of 44,444 referrals to speech and language therapy, 5,254 referrals were included in the stroke and overall subgroup analyses. Referrals were 55.1% male, with a median age of 71 years. More than half (56.1%) of these referrals were for dysphagia. Referrals decreased during the COVID-19 pandemic but began to recover from 2021 onwards. The time on the SLT caseload has increased over the years from a median of 14 days (interquartile range [IQR] 0-56) in 2018 to 20 days (IQR: 3-81) in 2022. While there were more referrals to SLT services for assessment and management of dysphagia than for communication in the overall population, in the stroke subgroup, referrals for communication disorders outnumbered referrals for dysphagia from 2020 onwards. Additionally, the severity of impairment on referral increased over the years. CONCLUSION: Real-world data indicates that referrals to SLT services are changing over time to include more complex and severely impaired patients, with a demand for both swallowing and communication disorders. These findings should inform staff allocation and remodelling of education/training for SLTs to better meet clinical and public health needs. The retrospective nature of this study limits the strength and generalisability of these data, and this topic warrants further investigation.

Integrating analysis of proteome profile and drug screening identifies therapeutic potential of MET pathway for the treatment of malignant peripheral nerve sheath tumor.

BACKGROUND: Malignant peripheral nerve sheath tumor (MPNST) is an aggressive sarcoma with a poor prognosis that requires novel therapeutic agents. Proteome information is useful for identifying new therapeutic candidates because it directly reflects the biological phenotype. Additionally, in vitro drug screening is an effective tool to identify candidate drugs for common cancers. Hence, we attempted to identify novel therapeutic candidates for MPNST by integrating proteomic analysis and drug screening. METHODS: We performed comprehensive proteomic analysis on 23 MPNST tumor samples using liquid chromatography - tandem mass spectrometry to identify therapeutic targets. We also conducted drug screening of six MPNST cell lines using 214 drugs. RESULTS: Proteomic analysis revealed that the MET and IGF pathways were significantly enriched in the local recurrence/distant metastasis group of MPNST, whereas drug screening revealed that 24 drugs showed remarkable antitumor effects on the MPNST cell lines. By integrating the results of these two approaches, MET inhibitors, crizotinib and foretinib, were identified as novel therapeutic candidates for the treatment of MPNST. CONCLUSIONS: We successfully identified novel therapeutic candidates for the treatment of MPNST, namely crizotinib and foretinib, which target the MET pathway. We hope that these candidate drugs will contribute to the treatment of MPNST.

A Safe Way to Administer Drugs Through a Nutrition Tube-The Simple Suspension Method.

The simple suspension method (SSM), developed by Kurata in 1997, is a way to suspend tablets and capsules in warm water for decay and suspension prior to their administration. This method is safe and has various advantages such as the avoidance of tube clogging and the loss of the drug. This study aimed to investigate whether a higher percentage of commonly used drugs could pass through nutrition tubes effectively using SSM, relative to that using the conventional crushing method. A tablet or capsule was inserted into a 20 mL syringe with warm water (at 55 °C). After 10 min, it was shaken in the syringe. The suspension liquid was injected into tubes of the following sizes: 8 Fr, 10 Fr, 12 Fr, 14 Fr, 16 Fr, and 18 Fr. A total of 3686 tablets and 432 capsules that are frequently used in Japan were tested. Using SSM, 3377 (91.6%) tablets and 359 (83.1%) capsules disintegrated within 10 min and passed through the tube without clogging it in the tube passage test. With the conventional crushing method, 2117 tablets (57.4%) and 272 capsules (63.0%) could be crushed. SSM reduced the risk of tube clogging and drug loss with more drugs than that with the conventional crushing method. The number of drugs indicated for administration by SSM is greater than that indicated by the conventional crushing method. Further studies are needed to consider its utility compared to conventional methods for dysphagia patients in clinical settings.

The oncogene KRAS promotes cancer cell dissemination by stabilizing spheroid formation via the MEK pathway.

BACKGROUND: Peritoneal dissemination is a critical prognostic factor in ovarian cancer. Although stabilized spheroid formation promotes cancer cell peritoneal dissemination in ovarian cancer, the associated oncogenes are unknown. In this study, we assessed the role of the KRAS oncogene in ovarian cancer cell dissemination, focusing on the stability of cells in spheroid condition, as well as the modulation of intracellular signaling following spheroid transformation. METHODS: We used ID8, a murine ovarian cancer cell line, and ID8-KRAS, an oncogenic KRAS (G12 V)-transduced ID8 cell line in this study. Spheroid-forming (3D) culture and cell proliferation assays were performed to evaluate the growth characteristics of these cells. cDNA microarray analysis was performed to identify genes involved in KRAS-associated signal transduction in floating condition. A MEK inhibitor was used to evaluate the effect on cancer peritoneal dissemination. RESULTS: Cell viability and proliferation in monolayer (2D) cultures did not differ between ID8 and ID8-KRAS cells. However, the proportions of viable and proliferating ID8-KRAS cells in 3D culture were approximately 2-fold and 5-fold higher than that of ID8, respectively. Spheroid-formation was increased in ID8-KRAS cells. Analysis of peritoneal floating cells obtained from mice intra-peritoneally injected with cancer cells revealed that the proportion of proliferating cancer cells was approximately 2-fold higher with ID8-KRAS than with ID8 cells. Comprehensive cDNA microarray analysis revealed that pathways related to cell proliferation, and cell cycle checkpoint and regulation were upregulated specifically in ID8-KRAS cells in 3D culture, and that some genes partially regulated by the MEK-ERK pathway were upregulated only in ID8-KRAS cells in 3D culture. Furthermore, a MEK inhibitor, trametinib, suppressed spheroid formation in 3D culture of ID8-KRAS cells, although trametinib did not affect 2D-culture cell proliferation. Finally, we demonstrated that trametinib dramatically improved the prognosis for mice with ID8-KRAS tumors in an in vivo mouse model. CONCLUSIONS: Our data indicated that KRAS promoted ovarian cancer dissemination by stabilizing spheroid formation and that the MEK pathway is important for stabilized spheroid formation. Disruption of spheroid formation by a MEK inhibitor could be a therapeutic target for cancer peritoneal dissemination.

Roles of the PDZ-binding motif of HPV 16 E6 protein in oncogenic transformation of human cervical keratinocytes.

The high-risk human papillomavirus E6 proteins have been shown to interact with and lead to degradation of PDZ-domain-containing proteins through its carboxy-terminal motif. This PDZ-binding motif plays important roles in transformation of cultured cells and carcinogenesis of E6-transgenic mice. However, its biological effects on the natural host cells have not been elucidated. We have examined its roles in an in vitro carcinogenesis model for cervical cancer, in which E6 and E7 together with activated HRAS (HRASG12V ) can induce tumorigenic transformation of normal human cervical keratinocytes. In this model, E6Δ151 mutant, which is defective in binding to PDZ domains, almost lost tumorigenic ability, whereas E6SAT mutant, which is defective in p53 degradation showed activity close to wild-type E6. Interestingly, we found decreased expression of PAR3 in E6-expressing cells independently of E6AP, which has not been previously recognized. Therefore, we knocked down several PDZ-domain containing proteins including PAR3 in human cervical keratinocytes expressing E7, HRASG12V and E6Δ151 to examine whether depletion of these proteins can restore the tumorigenic ability. Single knockdown of SCRIB, MAGI1 or PAR3 significantly but partially restored the tumorigenic ability. The combinatorial knockdown of SCRIB and MAGI1 cooperatively restored the tumorigenic ability, and additional depletion of PAR3 further enhanced the tumorigenic ability surpassing that induced by wild-type E6. These data highlight the importance of the carboxy-terminal motif of the E6 protein and downregulation of PAR3 in tumorigenic transformation of human cervical keratinocytes.

Initial limited three-level thin-section computed tomography scorings predict the prognosis of acute/subacute interstitial pneumonia in patients with dermatomyositis.

OBJECTIVES: We investigated the prediction of outcomes of patients with dermatomyositis with acute/subacute interstitial pneumonia (DM-A/SIP) on the basis of chest computed tomography (CT) images. METHODS: In 20 patients with DM-A/SIP (13 survivors; seven deaths), the relationships between prognostic outcomes and chest high-resolution CT (HRCT) findings or limited three-level thin-section CT scoring on the first examination were retrospectively investigated. RESULTS: No significant difference was noted in chest HRCT findings between the survivor group and death group. The ground-glass opacity (GGO) scores of the right upper and middle lobes and left upper lobe, and the fibrosis score of the right middle lobe were significantly higher in the death group than in the survivor group (p = 0.01, 0.001, 0.02, and 0.02, respectively). The influence of the GGO score of the right middle lobe on death from IP was the strongest among the items examined, and it was independently significant (p = 0.01). A right middle lobe GGO score of ≥3 (GGO ≥ 25% of the lobe) was determined to be the best cut-off value for a poor prognosis (sensitivity: 85.7%, specificity: 85.7%), and the survival rate after 24 weeks was significantly lower in patients with a right middle lobe GGO score of ≥3 (survival rate: 0.0%) than in those with a score of< 3 (92.9%) (p < 0.0001). CONCLUSIONS: The prognosis of patients with DM-A/SIP was poor when the range of right middle lobe GGO was 25% or higher on limited three-level thin-section CT.

Modified medication use in dysphagia: the effect of thickener on drug bioavailability-a systematic review.

INTRODUCTION: Dysphagia is associated with long-term conditions including strokes, dementia, Parkinson's disease and frailty. Dysphagia affects 30-40% of the population aged over 65 years-old. Adults with dysphagia often experience long-term conditions requiring multiple medications (often > 5) to manage these. The thickening of liquids is a common compensatory strategy in dysphagia management. Studies suggest that immersion in thickened liquids affects medicines' solubility in vitro. Clinicians and pharmacists are unaware of the pharmacokinetic/therapeutic effects of thickened liquids on oral medicines. We conducted a systematic review of existing literature on thickeners' effects on drug bioavailability. METHODOLOGY: We performed a literature search of MEDLINE & EMBASE. Search terms included: dysphagia/thickened diet (EMBASE only)/ bioavailability or absorption of medicines or pharmacokinetics; excluded: NG feeds/animal studies. STUDIES INCLUDED: all genders, countries, > 18 years, community and hospital settings. PRISMA guidance was followed. RESULTS: Five hundred seventy results were found, and 23 articles identified following the reference list review. Following an abstract and full-text review, 18 were included. Most articles evaluated thickeners on dissolution profiles in-vitro, with a few investigating in-vivo. Most studies were single-centre prospective studies identifying that thickeners generally affect dissolution rates of medications. Few studies assessed bioavailability or used clinical outcomes. CONCLUSION: Dysphagia and polypharmacy are common in older adults, but little is known about the effects of altering liquid viscosity on the therapeutic effect of most medications. Further larger-scale studies are required to evaluate the therapeutic impact of thickener, on a bigger range of medications, factoring in other variables such as type of thickener, viscosity of thickener and duration of immersion.

The Potential Role of Angiotensin-Converting Enzyme Inhibitors and Beta-Blockers in Reducing Pneumonia Severity in Older Adults.

Background Understanding the impact of pharmacological therapy on pneumonia severity is crucial for effective clinical management. The impact of angiotensin-converting enzyme inhibitors (ACEis) and beta-blockers (BBs) on pneumonia severity remains unknown, warranting further investigation. Methodology This retrospective study examined the hospital records of inpatients (≥75 years) admitted with community-acquired pneumonia in 2021. Pneumonia severity associated with the use of pre-established ACEi and BB therapy was documented using CURB-65 (confusion, uraemia, respiratory rate, blood pressure, age ≥65 years) and pneumonia severity index (PSI) scores. Descriptive statistics and multivariable linear regression were used to analyse differences across BB therapy, ACEi therapy, their combination, or neither (control group). Results A total of 803 patient records were examined, of whom 382 (47.6%) were male and 421 (52.4%) were female. Sample sizes for each group were as follows: control (n = 492), BB only (n = 185), ACEi only (n = 68), and BB + ACEi (n = 58). Distribution of aspiration pneumonia (AP) versus non-AP for each group, respectively, was control (21.1% vs. 78.9%), BB only (9.7% vs. 90.3%), ACEi only (7.3% vs. 92.7%), and ACEi + BB (12.1% vs. 87.9%). No significant differences in PSI and CURB-65 scores were found between intervention groups even after controlling for patient characteristics and irrespective of AP or non-AP aetiology. Patients with AP had significantly higher CURB-65 (p = 0.026) and PSI scores (p = 0.044) compared to those with non-AP. Conclusions Pre-prescribed ACEi or BB therapy did not appear to be associated with differences in pneumonia severity. There were no differences in pneumonia severity scores with ACEi and BB monotherapy or combined ACEi and BB therapy.

Prognostic factors of poor outcomes in pneumonia in older adults: aspiration or frailty?

PURPOSE: Little is known about the long-term and functional prognoses of older adults with pneumonia, which complicates their management. There is a common belief that aspiration is a poor prognostic factor; however, the diagnosis of aspiration pneumonia (AP) lacks consensus criteria and is mainly based on clinical characteristics typical of the frailty syndrome. Therefore, the poor prognosis of AP may also be a result of frailty rather than aspiration. This study investigated the impact of AP and other prognostic factors in older patients with pneumonia. METHODS: We performed a retrospective cohort study of patients aged 75 years and older, admitted with pneumonia in 2021. We divided patients according to their initial diagnosis (AP or non-AP), compared outcomes using Kaplan-Meier curves, and used logistic regression to identify independent prognostic factors. RESULTS: 803 patients were included, with a median age of 84 years and 52.7% were male. 17.3% were initially diagnosed with AP. Mortality was significantly higher in those diagnosed with AP than non-AP during admission (27.6% vs 19.0%, p = 0.024) and at 1 year (64.2% vs 53.1%, p = 0.018), with survival analysis showing a median survival time of 62 days and 274 days in AP and non-AP, respectively (χ2 = 9.2, p = 0.002). However, the initial diagnosis of AP was not an independent risk factor for poor prognosis in multivariable analysis. Old age, frailty and cardio-respiratory comorbidities were the main factors associated with death. CONCLUSION: The greater mortality in AP may be a result of increased frailty rather than the diagnosis of aspiration itself. This supports our proposal for a paradigm shift from making predictions based on the potentially futile labelling of AP or non-AP, to considering frailty and overall condition of the patient.

Decisions on eating and drinking in older adults admitted with pneumonia and referred for swallowing difficulties.

PURPOSE: Older patients with pneumonia are commonly restricted from oral intake due to concerns towards aspiration. Eating and drinking with acknowledged risks (EDAR) is a shared decision-making process emphasising patient comfort. As part of our project to find the barriers and facilitators of EDAR, we aimed for this initial study to see how frequently EDAR was selected in practice. METHODS: We performed a retrospective cohort study at an acute hospital where EDAR was initially developed, of patients aged ≥ 75 years-old admitted with pneumonia and referred to speech and language therapy. RESULTS: Out of 216 patients, EDAR decisions were made in 14.4%. The EDAR group had a higher 1-year mortality than the modified/normal diet groups (p < 0.001). Pneumonia recurrence rate did not differ significantly between the groups (p = 0.070). CONCLUSION: EDAR decisions were comparatively less common and most were associated with end-of-life care. Underlying reasons for the low EDAR application rate must be investigated to maximise patient autonomy and comfort as intended by EDAR while minimising staff burden.

Nodular pulmonary amyloidosis diagnosed by ultrasound-guided percutaneous needle biopsy.

Pulmonary amyloidosis is characterized by extracellular deposition of fibrous protein called amyloid in the lungs and has three subtypes: nodular, diffuse, and tracheobronchial amyloidosis. Pulmonary nodular amyloidosis can mimic other lung diseases including infectious diseases, metastatic lung tumors, sarcoidosis, and pulmonary hyalinizing granuloma. A biopsy of the lesion is essential for a definitive diagnosis. Herein, we report the case of a 66-year-old man who presented for shortness of breath on exertion and was diagnosed with nodular pulmonary amyloidosis on ultrasound-guided percutaneous needle biopsy. A chest X-ray and computed tomography (CT) revealed bilateral slowly growing multiple calcified pulmonary nodules and cavities. Malignancy was suspected based on 18F-fluoro-deoxyglucose (18F-FDG) positron emission tomography/CT (PET/CT) images. An ultrasound-guided percutaneous needle biopsy was performed, and histopathologic examination of the lesion confirmed nodular pulmonary amyloidosis. This case highlights the importance of considering nodular pulmonary amyloidosis in the differential diagnosis of pulmonary nodules with increased uptake of 18F-FDG on PET/CT and the utility of ultrasound-guided needle biopsy in the definitive diagnosis.

"Diagnose, Treat, and SUPPORT". Clinical competencies in the management of older adults with aspiration pneumonia: a scoping review.

BACKGROUND: Aspiration pneumonia in older adults is increasingly common, with a high care burden and morbidity. However, clinical competencies in its management have not been developed, and healthcare professionals struggle on how to care for these patients with multimodal treatment needs. Therefore, we conducted a scoping review to investigate what is known about the desired clinical competencies for the management of older adults with aspiration pneumonia, to utilise in clinical practice, education, and future research. METHODS: First, we defined aspiration pneumonia according to a preliminary search. We then searched the literature on MEDLINE and CINAHL, focusing on studies involving patients aged 65 years old and older diagnosed with aspiration pneumonia. All settings were included, with the exception of intensive care units. Publication dates were limited to January 2011 to July 2022 and languages to English and Japanese. The extracted data were used to refine the preliminary competency framework developed by the Japan Aspiration pneumonia inter-Professional team Educational Program (JAPEP) in preparation of this study. RESULTS: Ninety-nine studies were included. Following data extraction from these studies, 3 competencies were renamed, and 3 new competencies were added, to create a list of 12 competencies. These were Diagnosis, Treatment, Swallow Assessment, Underlying condition management, Nutrition, Oral management, Rehabilitation, Multidisciplinary team, Decision making, Prevention, Prognosis, and Palliative care. CONCLUSIONS: Our scoping review identified 12 clinical competencies required in the management of older adults with aspiration pneumonia, outlined in the phrase 'Diagnose, Treat and SUPPORT'. We encourage healthcare professionals to share these competencies as a team to identify areas of unmet need and improve their patient care, with an emphasis on supportive care.

Lack of Physician-Dentist Collaboration in Aspiration Pneumonia Prevention.

This opinion paper addresses the challenges and future directions for preventing aspiration pneumonia in Japan's rapidly aging population. It highlights the increasing proportion of elderly individuals and the associated rise in health issues like decreased swallowing function, a risk factor for aspiration pneumonia. The paper emphasizes the effectiveness of dentist-provided oral care in preventing this condition but notes the lack of collaboration between dentists and physicians in Japan's clinical practice. Key challenges identified include the scarcity of full-time hospital dentists, insufficient communication between physicians and dentists, limited patient understanding and motivation regarding oral care, and a lack of training in geriatric dentistry. The paper advocates for enhanced awareness among healthcare professionals and patients, increased hospital dentists, and improved collaboration mechanisms, particularly in light of recent positive changes in insurance reimbursement policies for elderly oral care.

Establishment and characterization of NCC-LMS3-C1: a novel patient-derived cell line of leiomyosarcoma.

Leiomyosarcoma (LMS) is an aggressive mesenchymal malignancy, which originates from the smooth muscle cells or from the precursor mesenchymal stem cells that potentially differentiate into smooth muscle cells. LMS is one of the most common sarcomas. LMS has genomic instability, reflecting complex and unbalanced karyotypes, and the cytogenetic and molecular changes in LMS are not consistent. The standard treatment of the primary LMS is complete resection, and the metastasis is often observed even after curative surgery. Patient-derived cancer models are a key bioresource to develop a novel therapy, and we aimed to establish and characterize a novel cell line for LMS. We established a cell line from tumor tissues of the patient with LMS and named it NCC-LMS3-C1. We maintained NCC-LMS3-C1 cells for 12 months and passed them more than 30 times. Genome-wide copy number analysis demonstrated that NCC-LMS3-C1 cells harbored genetic abnormalities. NCC-LMS3-C1 cells exhibited aggressive phenotypes such as continuous growth, spheroid formation, and invasion in the tissue culture condition, which may reflect the clinical behaviors of LMS. We performed a drug screening using NCC-LMS3-C1 cells and found that four anti-cancer agents, such as bortezomib, dasatinib, mitoxantrone, and romidepsin, had remarkable anti-proliferative effects on NCC-LMS3-C1 cells. We conclude that NCC-LMS3-C1 cells will be a useful resource for the study of LMS.

Profilin 2 isoform expression is associated with lung metastasis of colorectal cancer according to a comprehensive gene expression study using a mouse model.

Lung metastasis is the second most common type of metastasis in colorectal cancer. Specific treatments for lung metastasis have not been developed since the underlying mechanisms are poorly understood. The present study aimed to elucidate the molecular basis of lung metastasis in colorectal cancer. In a mouse model, cell lines that were highly metastatic to the lungs were established by injecting colorectal cancer cells through the tail vein and removing them from the lungs. Differential gene expression comparing the transfected cells with their parental cells was investigated using DNA microarrays. The results were functionally interpreted using gene enrichment analysis and validated using reverse transcription-quantitative PCR (RT-qPCR). The isoforms of the identified genes were examined by melting curve analysis. The present study established colorectal cancer cell lines that were highly metastatic to the lungs. DNA microarray experiments revealed that genes (N-cadherin, VE-cadherin, Six4, Akt and VCAM1) involved in motility, proliferation and adhesion were upregulated, and genes (tissue inhibitor of metalloproteinase-3 and PAX6) with tumor-suppressive functions were downregulated in metastatic cells. Profilin 2 (PFN2) expression was upregulated in multiple metastatic cell lines using RT-qPCR. Two PFN2 isoforms were overexpressed in metastatic cells. In vitro and in vivo models were established and genes associated with lung metastasis were identified to overcome the heterogeneity of the disease. Overall, aberrant PFN2 expression is unreported in lung metastasis in colorectal cancer. In the present study, two PFN2 isoforms with differential tissue distribution were upregulated in metastatic cells, suggesting that they promote lung metastasis in colorectal cancer.

Establishment and characterization of NCC-DFSP5-C1: a novel patient-derived dermatofibrosarcoma protuberans cell line.

Dermatofibrosarcoma protuberans (DFSP) is the most prevalent dermal sarcoma, characterized by the presence of the fusion of the collagen type I alpha 1 (COL1A1) gene with the platelet-derived growth factor beta chain (PDGFB) gene. Although PDGF receptor inhibitor imatinib mesylate was approved for the treating patients with unresectable or metastatic DFSP, disease progression was shown in 9.2% of the patients. Therefore, developing novel therapeutic strategies is crucial for improving the prognosis of DFSP. Patient-derived cell lines play a vital role in preclinical studies; however, only a limited number of DFSP cell lines are currently available in public cell banks. Here, we successfully established a novel DFSP cell line (NCC-DFSP5-C1) using surgically resected tumor tissue from a patient with DFSP. NCC-DFSP5-C1 cells were confirmed to carry the COL1A1-PDGFB translocation and maintain the same mutation as the original tumor tissue. They exhibited consistent growth, formed spheroids, and were invasive. By screening a drug library using NCC-DFSP5-C1 and four previously established DFSP cell lines, we identified anti-cancer drugs that inhibit DFSP cell proliferation. Our observations suggest that the NCC-DFSP5-C1 cell line holds promise as a valuable tool for conducting fundamental and preclinical studies for DFSP.

Establishment and characterization of NCC-PMP2-C1: a novel patient-derived cell line of pseudomyxoma peritonei with signet ring cells.

Pseudomyxoma peritonei (PMP) is a rare phenomenon, characterized by accumulation of mucus in the abdominal cavity due to a mucinous neoplasm. Histologically, PMP is divided into three prognostic classes, namely low-grade mucinous carcinoma peritonei (LGMCP), high-grade mucinous carcinoma peritonei (HGMCP), and high-grade mucinous carcinoma peritonei with signet ring cells (HGMCP-S); HGMCP-S exhibits the worst prognosis. Complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy have been established as the standard therapy for PMP. However, 50% of patients with PMP experience a recurrence, and 30-40% are unable to receive the standard treatment due to invasive diseases. Therefore, novel therapies are required for their treatment. Although patient-derived cell lines are important tools for basic and pre-clinical research, PMP cell lines derived from patients with HGMCP-S have never been reported. Thus, we established a novel PMP cell line NCC-PMP2-C1, using surgically resected tumor tissue from a patient with HGMCP-S. NCC-PMP2-C1 cells were maintained for more than five months and passaged 30 times under culture conditions. NCC-PMP2-C1 cells exhibited multiple deletions and somatic mutations, slow growth, histological features, and dissemination of tumor cells in nude mice. Screening for the anti-proliferative effects of anti-cancer drugs on cells revealed that bortezomib, mubritinib, and romidepsin had a significant response against NCC-PMP2-C1 cells. Thus, the NCC-PMP2-C1 cell line is the first PMP cell line harboring signet ring cells and will be a valuable resource for basic and preclinical studies of HGMCP-S.