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1.
Asian J Endosc Surg ; 17(3): e13348, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38965686

ABSTRACT

Arterio-ureteral fistulas (AUFs), which are relatively rare but potentially life-threatening, require prompt diagnosis and treatment. We reported a case of AUFs following robot-assisted laparoscopic radical cystectomy (RARC) with extended pelvic lymph node dissection and ileal conduit urinary diversion for muscle-invasive bladder cancer, which resulted in massive hemorrhage. Urine leaked from the anastomosis between the ureter, and the end of the ileal conduit was infected, which resulted in an AUF between the pseudoaneurysm of the right common iliac artery and the ureter. The AUF was managed successfully by vascular intervention with an arterial stent graft.


Subject(s)
Aneurysm, False , Cystectomy , Iliac Artery , Laparoscopy , Robotic Surgical Procedures , Ureteral Diseases , Urinary Fistula , Vascular Fistula , Humans , Cystectomy/adverse effects , Aneurysm, False/etiology , Aneurysm, False/surgery , Urinary Fistula/etiology , Urinary Fistula/surgery , Ureteral Diseases/etiology , Ureteral Diseases/surgery , Iliac Artery/surgery , Vascular Fistula/etiology , Vascular Fistula/surgery , Male , Postoperative Complications/surgery , Postoperative Complications/etiology , Urinary Bladder Neoplasms/surgery , Aged , Middle Aged
2.
Front Robot AI ; 11: 1363243, 2024.
Article in English | MEDLINE | ID: mdl-38894894

ABSTRACT

Social technology can improve the quality of social lives of older adults (OAs) and mitigate negative mental and physical health outcomes. When people engage with technology, they can do so to stimulate social interaction (stimulation hypothesis) or disengage from their real world (disengagement hypothesis), according to Nowland et al.'s model of the relationship between social Internet use and loneliness. External events, such as large periods of social isolation like during the COVID-19 pandemic, can also affect whether people use technology in line with the stimulation or disengagement hypothesis. We examined how the COVID-19 pandemic affected the social challenges OAs faced and their expectations for robot technology to solve their challenges. We conducted two participatory design (PD) workshops with OAs during and after the COVID-19 pandemic. During the pandemic, OAs' primary concern was distanced communication with family members, with a prevalent desire to assist them through technology. They also wanted to share experiences socially, as such OA's attitude toward technology could be explained mostly by the stimulation hypothesis. However, after COVID-19 the pandemic, their focus shifted towards their own wellbeing. Social isolation and loneliness were already significant issues for OAs, and these were exacerbated by the COVID-19 pandemic. Therefore, such OAs' attitudes toward technology after the pandemic could be explained mostly by the disengagement hypothesis. This clearly reflect the OA's current situation that they have been getting further digitally excluded due to rapid technological development during the pandemic. Both during and after the pandemic, OAs found it important to have technologies that were easy to use, which would reduce their digital exclusion. After the pandemic, we found this especially in relation to newly developed technologies meant to help people keep at a distance. To effectively integrate these technologies and avoid excluding large parts of the population, society must address the social challenges faced by OAs.

3.
J Pharm Health Care Sci ; 10(1): 33, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38926760

ABSTRACT

BACKGROUND: Anamorelin, a drug to treat cancer cachexia, binds to ghrelin receptors and improves body weight and appetite. In clinical trials in Japan, patients experienced a 10.7% frequency of stimulant conduction system depression as a severe side effect. Although rare, anamorelin sometimes causes fatal arrhythmias. Because patients with cancer cachexia are often underweight, data on the safety of anamorelin in obese patients are lacking. We report a case of QT interval prolongation after anamorelin administration to an obese patient with non-small cell lung cancer. CASE PRESENTATION: A female patient with a body mass index of 30 kg/m2 underwent immunotherapy for lung adenocarcinoma. She presented with severe weight loss, anorexia, and fatigue. She had no history of heart disease. On day 12, after administration of anamorelin 100 mg once daily, the patient developed nausea, diarrhea, and anorexia, which were considered cancer immunotherapy-induced immune-related adverse events, and she was admitted to the hospital. An electrocardiogram (ECG) on admission showed a QTc interval of 502 ms. On admission, her hepatic function was Child-Pugh class B, and anamorelin was discontinued the next day. On day 3 after anamorelin discontinuation, the QTc interval was prolonged by up to 557 ms, then decreased to 490 ms on day 6, and improved to 450 ms on day 16. Re-administration of anamorelin was avoided. CONCLUSIONS: When administering anamorelin to obese patients, we should be aware of the potential for stimulatory conduction system depression, as in underweight patients. Therefore, we should monitor patients by ECG from the early stages of anamorelin administration. Anamorelin is lipophilic, and its volume of distribution is increased in obese patients. Consequently, obese patients may continue to have QT interval prolongation after discontinuation of anamorelin, requiring long-term side-effect monitoring.

4.
Int J Clin Oncol ; 29(7): 1019-1026, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38797782

ABSTRACT

BACKGROUND: Nivolumab plus ipilimumab (NIVO + IPI) is the first-line treatment for patients with metastatic renal cell carcinoma (mRCC). While approximately 40% of patients treated with NIVO + IPI achieve a durable response, 20% develop primary resistance with severe consequences. Therefore, there is a clinical need for criteria to select patients suitable for NIVO + IPI therapy to optimize its therapeutic efficacy. Accordingly, our aim was to evaluate the association between candidate biomarkers measured before treatment initiation and survival. METHODS: This was a multi-institutional, retrospective, cohort study of 183 patients with mRCC treated with systematic therapies between August 2015 and July 2023. Of these, 112 received NIVO + IPI as first-line therapy: mean age, 68 years; men, 83.0% (n = 93), and clear cell histology, 80.4% (n = 90). Univariable and multivariable analyses were used to evaluate associations between biomarkers and survival. RESULTS: On univariate analysis, high C-reactive protein and systemic index, a high neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio, and a low lymphocyte-to-monocyte ratio (LMR) were associated with shorter overall survival (OS). On multivariable analysis, a LMR ≤ 3 was retained as an independent factor associated to shorter OS with the highest accuracy (C-index, 0.656; hazard ratio, 7.042; 95% confidence interval, 2.0-25.0; p = 0.002). CONCLUSION: A low LMR may identify patients who would be candidate for NIVO + IPI therapy for mRCC.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Carcinoma, Renal Cell , Ipilimumab , Kidney Neoplasms , Lymphocytes , Monocytes , Nivolumab , Humans , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/secondary , Ipilimumab/administration & dosage , Ipilimumab/therapeutic use , Nivolumab/administration & dosage , Nivolumab/therapeutic use , Male , Aged , Female , Retrospective Studies , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Kidney Neoplasms/mortality , Kidney Neoplasms/blood , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphocytes/pathology , Biomarkers, Tumor/blood , Aged, 80 and over
5.
Int J Urol ; 2024 May 09.
Article in English | MEDLINE | ID: mdl-38722221

ABSTRACT

OBJECTIVES: The JAVELIN Bladder 100 phase 3 trial showed that avelumab first-line maintenance + best supportive care significantly prolonged overall survival and progression-free survival versus best supportive care alone in patients with advanced urothelial carcinoma who were progression-free following first-line platinum-based chemotherapy. We report findings from J-AVENUE (NCT05431777), a real-world study of avelumab first-line maintenance therapy in Japan. METHODS: Medical charts of patients with advanced urothelial carcinoma without disease progression following first-line platinum-based chemotherapy, who received avelumab maintenance between February and November 2021, were reviewed. Patients were followed until June 2022. The primary endpoint was patient characteristics; secondary endpoints included time to treatment failure and progression-free survival. RESULTS: In 79 patients analyzed, median age was 72 years (range, 44-86). Primary tumor site was upper tract in 45.6% and bladder in 54.4%. The most common first-line chemotherapy regimen was cisplatin + gemcitabine (63.3%). Median number of chemotherapy cycles received was four. Best response to chemotherapy was complete response in 10.1%, partial response in 58.2%, and stable disease in 31.6%. Median treatment-free interval before avelumab was 4.9 weeks. With avelumab first-line maintenance therapy, the disease control rate was 58.2%, median time to treatment failure was 4.6 months (95% CI, 3.3-6.4), and median progression-free survival was 6.1 months (95% CI, 3.6-9.7). CONCLUSIONS: Findings from J-AVENUE show the effectiveness of avelumab first-line maintenance in patients with advanced urothelial carcinoma in Japan in clinical practice, with similar progression-free survival to JAVELIN Bladder 100 and previous real-world studies, supporting its use as a standard of care.

6.
Sci Rep ; 14(1): 11561, 2024 05 21.
Article in English | MEDLINE | ID: mdl-38773300

ABSTRACT

Mitochondrial diseases are mainly caused by dysfunction of mitochondrial respiratory chain complexes and have a variety of genetic variants or phenotypes. There are only a few approved treatments, and fundamental therapies are yet to be developed. Leigh syndrome (LS) is the most severe type of progressive encephalopathy. We previously reported that apomorphine, an anti- "off" agent for Parkinson's disease, has cell-protective activity in patient-derived skin fibroblasts in addition to strong dopamine agonist effect. We obtained 26 apomorphine analogs, synthesized 20 apomorphine derivatives, and determined their anti-cell death effect, dopamine agonist activity, and effects on the mitochondrial function. We found three novel apomorphine derivatives with an active hydroxy group at position 11 of the aporphine framework, with a high anti-cell death effect without emetic dopamine agonist activity. These synthetic aporphine alkaloids are potent therapeutics for mitochondrial diseases without emetic side effects and have the potential to overcome the low bioavailability of apomorphine. Moreover, they have high anti-ferroptotic activity and therefore have potential as a therapeutic agent for diseases related to ferroptosis.


Subject(s)
Aporphines , Leigh Disease , Mitochondria , Leigh Disease/drug therapy , Humans , Mitochondria/drug effects , Mitochondria/metabolism , Aporphines/pharmacology , Aporphines/chemistry , Aporphines/chemical synthesis , Aporphines/therapeutic use , Fibroblasts/drug effects , Fibroblasts/metabolism , Apomorphine/pharmacology , Apomorphine/therapeutic use , Apomorphine/analogs & derivatives , Dopamine Agonists/pharmacology , Dopamine Agonists/therapeutic use , Dopamine Agonists/chemistry , Alkaloids/pharmacology , Alkaloids/chemistry , Alkaloids/therapeutic use
7.
J Robot Surg ; 18(1): 154, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38564051

ABSTRACT

Robot-assisted partial nephrectomy (RAPN) has been shown to be a safe and effective method for treatment of small renal tumors, including clinical T1b renal cell carcinoma (RCC); however, the impact of RAPN for cT1b renal tumors on renal function is not well understood. In this retrospective study, 50 patients who underwent RAPN for cT1b renal tumors were evaluated for pre- and post-operative renal function and perioperative clinical factors. Renal function was assessed using the estimated glomerular filtration rate (eGFR) at baseline and on postoperative days (POD) 1, 7, 30, and 180.A significant renal functional decline was defined as ≥ 15% reduction in eGFR at POD180 compared with eGFR at baseline. Logistic regression analyses were used to identify risk factors for renal function decline, including age, sex, RENAL nephrometry score, operative time, and estimated blood loss. The median patient age was 62 years, and the median tumor diameter and RENAL nephrometry score were 44 mm (IQR 43-50) and 8 (IQR 7-9), respectively. Of these patients, 16 (36%) showed a significant renal functional decline at POD 180. In the multivariate analysis, the L component of the RENAL nephrometry score and an estimated blood loss of 200 mL or more were identified as significant risk factors for renal functional decline. These findings suggest that the preoperatively definable L component of the RENAL nephrometry score and intraoperative blood loss, which may be modifiable factors, play significant roles in post-RAPN renal function decline.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Robotic Surgical Procedures , Robotics , Humans , Middle Aged , Retrospective Studies , Robotic Surgical Procedures/methods , Nephrectomy/adverse effects , Kidney/surgery , Carcinoma, Renal Cell/surgery , Kidney Neoplasms/surgery
8.
Anal Sci ; 40(5): 925-934, 2024 May.
Article in English | MEDLINE | ID: mdl-38528254

ABSTRACT

Stereoinversion of Ser residues within proteins, which has been identified in long-lived proteins, influences protein function. To quantify the stereoinversion of Ser residues, we investigated the potential adaptation of our direct peptide analytical method originally established for analyzing the isomerization of asparaginyl/aspartyl residues. Peptide pairs containing L-Ser or D-Ser residues with lengths of four or five residues were synthesized. Separation conditions for these peptide pairs were systematically examined by precisely adjusting the pH of the elution solvent using reverse-phase high-performance liquid chromatography (HPLC). Optimal separation conditions were successfully developed for all peptide pairs, enabling the direct quantification of Ser residue stereoinversion through a single HPLC run. Subsequently, the degree of Ser stereoinversion within the model peptide, Gly-Ser-Gly-Tyr, was determined using the method established in this study. Surprisingly, the stereoinversion of Ser residues occurred only when the absolute configurations of Ser and Tyr residues of the peptide differed from each other, whereas no stereoinversion was observed when their absolute configurations were identical. The experiments using peptides similar to the model peptide reveal that both the N-terminal amino group and the hydroxyl group of the C-terminal Tyr residue are involved in the stereoinversion of the Ser residue. By applying a simple method to quantify the stereoinversion of Ser residues, valuable insights into the mechanisms governing these stereoinversions were obtained.

9.
Congenit Anom (Kyoto) ; 64(3): 91-98, 2024 May.
Article in English | MEDLINE | ID: mdl-38445786

ABSTRACT

To assess the risk of major birth defects after first-trimester exposure to carbocisteine and ambroxol during pregnancy, we conducted a prospective cohort study using counseling data for drug use during pregnancy provided by the Japan Drug Information Institute in Pregnancy and Toranomon Hospital. Counseling information, including drug usage and participants' demographic information, was collected between April 1988 and December 2017. Pregnancy outcome data, including major birth defects, were obtained using a questionnaire administered 1 month after delivery. The risks of major birth defects after first-trimester exposure to carbocisteine (n = 588) and ambroxol (n = 341) were compared with those of nonteratogenic drug use during the first trimester (n = 1525). The adjusted odds ratio (aORs) for major birth defects was calculated using a multiple logistic regression analysis adjusted for confounders. The incidence of major birth defects was 1.2% (7/588) and 2.1% (7/341) in the carbocisteine and ambroxol groups, respectively, which was comparable to the control group (26/1525, 1.7%). Results of multiple logistic regression demonstrated similar nonsignificant risks for both carbocisteine (aOR: 0.66, 95% confidence interval [CI]: 0.40-1.1, p = 0.11) and ambroxol (aOR: 1.1, 95% CI: 0.18-7.2, p = 0.88). No specific major birth defects were reported in the carbocisteine or ambroxol groups. This study demonstrated that carbocisteine and ambroxol exposure during the first trimester was not associated with an increased risk of major birth defects. These results could help in counseling for the use of these drugs during pregnancy and further alleviate anxiety in patients.


Subject(s)
Abnormalities, Drug-Induced , Ambroxol , Pregnancy Trimester, First , Humans , Pregnancy , Female , Ambroxol/adverse effects , Prospective Studies , Abnormalities, Drug-Induced/epidemiology , Abnormalities, Drug-Induced/etiology , Adult , Japan/epidemiology , Counseling , Pregnancy Outcome/epidemiology , Risk Factors , Incidence
10.
Sci Rep ; 14(1): 4820, 2024 02 27.
Article in English | MEDLINE | ID: mdl-38413694

ABSTRACT

Originally, apomorphine was a broad-spectrum dopamine agonist with an affinity for all subtypes of the Dopamine D1 receptor to the D5 receptor. We previously identified apomorphine as a potential therapeutic agent for mitochondrial diseases by screening a chemical library of fibroblasts from patients with mitochondrial diseases. In this study, we showed that apomorphine prevented ferroptosis in fibroblasts from various types of mitochondrial diseases as well as in normal controls. Well-known biomarkers of ferroptosis include protein markers such as prostaglandin endoperoxide synthase 2 (PTGS2), a key gene for ferroptosis-related inflammation PTGS2, lipid peroxidation, and reactive oxygen species. Our findings that apomorphine induced significant downregulation of PTSG2 and suppressed lipid peroxide to the same extent as other inhibitors of ferroptosis also indicate that apomorphine suppresses ferroptosis. To our knowledge, this is the first study to report that the anti-ferroptosis effect of apomorphine is not related to dopamine receptor agonist action and that apomorphine is a potent inhibitor of ferroptotic cell death independent of dopaminergic receptors.


Subject(s)
Ferroptosis , Mitochondrial Diseases , Humans , Apomorphine/pharmacology , Cyclooxygenase 2/genetics , Receptors, Dopamine D2/metabolism , Dopamine Agonists/pharmacology
11.
Int J Mol Sci ; 25(4)2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38397001

ABSTRACT

Nicotinamide adenine dinucleotide (NAD) is a cofactor in redox reactions and an essential mediator of energy metabolism. The redox balance between NAD+ and NADH affects various diseases, cell differentiation, and aging, and in recent years there has been a growing need for measurement techniques with improved accuracy. However, NAD(H) measurements, representing both NAD+ and NADH, have been limited by the compound's properties. We achieved highly sensitive simultaneous measurement of NAD+ and NADH under non-ion pairing, mobile phase conditions of water, or methanol containing 5 mM ammonium acetate. These were achieved using a simple pre-treatment and 7-min analysis time. Use of the stable isotope 13C5-NAD+ as an internal standard enabled validation close to BMV criteria and demonstrated the robustness of NAD(H) determination. Measurements using this method showed that brain NAD(H) levels correlate strongly with plasma NAD(H) levels in the same mouse, indicating that NAD(H) concentrations in brain tissue are reflected in plasma. As NAD(H) is involved in various neurodegenerative diseases and cerebral ischemia, as well as brain diseases such as mitochondrial myopathies, monitoring changes in NADH levels in plasma after drug administration will be useful for development of future diagnostics and therapeutics.


Subject(s)
Brain Diseases , NAD , Mice , Animals , NAD/metabolism , Chromatography, Liquid , Liquid Chromatography-Mass Spectrometry , Tandem Mass Spectrometry , Brain/metabolism , Oxidation-Reduction
12.
Case Rep Oncol ; 16(1): 621-627, 2023.
Article in English | MEDLINE | ID: mdl-37900835

ABSTRACT

A 66-year-old male was diagnosed with cT4N0M1b small-cell neuroendocrine carcinoma of the prostate. Four months after the administration of combined androgen blockade, multiple novel metastatic regions in the lung and liver and progression of bone metastasis were observed. The patient was referred to our hospital because of biochemical and radiographic progression after four cycles of docetaxel as a first-line therapy for castration-resistant prostate cancer. Transurethral resection of the prostate and hepatic biopsy revealed small-cell carcinoma with positive expression of neuroendocrine markers. The FoundationOne CDx next-generation sequencing test revealed several pathogenic variants, including BRCA2 (W1692fs*3), KEAP1 (R320W), and TP53 (C2385) mutation. After four cycles of chemotherapy with carboplatin plus etoposide (CE), the metastatic regions regressed markedly. The prostate-specific antigen (PSA) and neuron-specific enolase (NSE) level decreased by 96.9% and 91.6%, respectively. However, 2 months after the completion of four cycles of CE, elevation of tumor marker levels, and re-growth of the metastatic regions were observed. Although olaparib, a poly (ADP-ribose) polymerase inhibitor (PARPi), achieved a 45.2% decrease in NSE, the patient rejected to continue therapy because of G2 adverse events. After receiving an additional two cycles of CE and one cycle of cabazitaxel, the patient died because of cancer progression 24 months after the initial treatment for prostate cancer. Here, we present a case of BRCA2-altered small-cell neuroendocrine prostate cancer treated with both platinum-containing chemotherapy and PARPi. Both therapies achieved an initial response; however, durable responses were not obtained. Additional discussion regarding the optimal treatment strategy for BRCA-altered small-cell/neuroendocrine prostate cancer is required.

13.
J Cancer Res Clin Oncol ; 149(16): 15091-15094, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37688628

ABSTRACT

BACKGROUND: We report a case of diffuse large B-cell lymphoma that progressed rapidly after androgen deprivation therapy for prostate cancer in a patient with a history of IgG4-related disease. Estrogen has been reported to be a possible cause of acute exacerbations of malignant lymphoma only in mouse models. Therefore, its clinical significance has not been clarified. CASE PRESENTATION: This case report describes a 75-year-old man with prostate cancer who had IgG4-related disease. Hormone therapy was initiated to treat prostate cancer, but he developed dyspnea and back pain. A diagnosis was made of diffuse large B-cell lymphoma. Immunohistochemistry was positive for estrogen receptor ß, which led us to suspect rapid progression of diffuse large B-cell lymphoma due to estrogen suppression by gonadotropin-releasing hormone antagonists. Hormone therapy was discontinued, and the patient received R-CHOP therapy. Subsequently, the lymphoma masses shrunk, and the patient obtained remission. CONCLUSION: This case is the first report of clinical significance regarding the crucial role of estrogen and estrogen receptor ß in malignant lymphoma in a patient with IgG4-related disease. Our report aims to raise awareness of the need to carefully select treatment options for prostate cancer patients with IgG4-related disease or lymphoma.


Subject(s)
Immunoglobulin G4-Related Disease , Lymphoma, Large B-Cell, Diffuse , Prostatic Neoplasms , Male , Animals , Mice , Humans , Aged , Prostatic Neoplasms/complications , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/pathology , Androgen Antagonists/therapeutic use , Androgens/therapeutic use , Estrogen Receptor beta , Lymphoma, Large B-Cell, Diffuse/drug therapy , Estrogens , Cell Proliferation
14.
Curr Oncol ; 30(9): 8092-8110, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37754502

ABSTRACT

A recent approach to radiotherapy for prostate cancer is the administration of high doses of radiation to the prostate while minimizing the risk of side effects. Thus, image-guided radiotherapy utilizes advanced imaging techniques and is a feasible strategy for increasing the radiation dose. New radioactive particles are another approach to achieving high doses and safe procedures. Prostate brachytherapy is currently considered as a combination therapy. Spacers are useful to protect adjacent organs, specifically the rectum, from excessive radiation exposure.


Subject(s)
Prostatic Neoplasms , Radiotherapy, Intensity-Modulated , Male , Humans , Radiotherapy Dosage , Radiotherapy, Intensity-Modulated/methods , Prostatic Neoplasms/radiotherapy , Prostatic Neoplasms/etiology , Prostate/radiation effects , Rectum/radiation effects
15.
Langmuir ; 39(32): 11481-11489, 2023 Aug 15.
Article in English | MEDLINE | ID: mdl-37531551

ABSTRACT

Staphylococcus aureus α-hemolysin (αHL) is one of the most popular proteins in nanopore experiments within lipid membranes. Higher concentrations of αHL within the lipid membrane are desirable to enhance the mass transport capacity through nanopores. However, the reconstitution of αHL at high concentrations is associated with the problem of membrane lytic disruption. In this study, we present a method that effectively increases αHL concentration while maintaining membrane stability. This method is achieved by using phase-separated giant liposomes, where coexisting liquid-disordered (Ld) and liquid-ordered phases (Lo) are enriched in unsaturated lipids and saturated lipids with cholesterol (Chol), respectively. Fluorescence observation of αHL in liposomes revealed that the presence of Chol facilitates αHL insertion into the membrane. Despite the preferential localization of αHL in the Ld phase rather than the Lo phase, the coexistence of both Lo and Ld phases prevents membrane disruption in the presence of concentrated αHL. We have explained this stabilization mechanism considering the lower membrane tension exhibited by phase-separated liposomes compared to homogeneous liposomes. Under hypertonic conditions, we have successfully increased the local concentration of αHL by invagination of the lipid-only region in the Ld phase, leaving αHL behind. This method exhibits potential for the reconstitution of various nanochannels and membrane proteins that prefer the Ld phase over the Lo phase, thus enabling the production of giant liposomes at high concentrations and the replication of the membrane-crowding condition observed in cells.

16.
Int J Clin Oncol ; 28(11): 1530-1537, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37552353

ABSTRACT

BACKGROUND: Although nivolumab plus ipilimumab is the standard treatment for metastatic renal cell carcinoma (RCC), its efficacy and safety in older patients remain unclear. Therefore, this study aimed to assess the clinical outcomes of nivolumab plus ipilimumab for metastatic RCC in patients aged ≥ 75 years. METHODS: We enrolled 120 patients with metastatic RCC treated with nivolumab plus ipilimumab from August 2015 to January 2023. Objective response rates (ORRs) were compared between patients aged < 75 and ≥ 75 years. Progression-free survival (PFS), overall survival (OS), and adverse events were compared between the groups. Adverse events were evaluated according to the Response Evaluation Criteria in Solid Tumors 1.1. RESULTS: Among the patients, 57 and 63 were classified as intermediate and poor risk, respectively, and one could not be classified. The median follow-up duration after the initiation of treatment was 16 months. The patient characteristics between the groups, except for age, were not significantly different. Intergroup differences in ORR (42% vs. 40%; p = 0.818), PFS (HR: 0.820, 95% CI 0.455-1.479; p = 0.510), and median OS (HR: 1.492, 95% CI 0.737-3.020; p = 0.267) were not significant. The incidence of adverse events (50% vs. 67%; p = 0.111) and nivolumab plus ipilimumab discontinuation due to adverse events was not significantly different between the groups (14% vs. 13%; p = 0.877). CONCLUSIONS: The effectiveness of nivolumab plus ipilimumab was comparable between patients with metastatic RCC aged < 75 and those ≥ 75 years with respect to their ORRs, PFS, OS, and adverse event rates.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Aged , Carcinoma, Renal Cell/pathology , Nivolumab/adverse effects , Ipilimumab/adverse effects , Kidney Neoplasms/pathology , Progression-Free Survival , Antineoplastic Combined Chemotherapy Protocols/adverse effects
17.
Cancer Med ; 12(16): 16837-16845, 2023 08.
Article in English | MEDLINE | ID: mdl-37403728

ABSTRACT

BACKGROUND: Nivolumab plus ipilimumab (NIVO+IPI) is the first-line treatment for patients with metastatic renal cell carcinoma (mRCC). Approximately 40% of patients achieve a durable response; however, 20% develop primary resistant disease (PRD) to NIVO+IPI, about which little is known in patients with mRCC. Therefore, this investigation aimed to evaluate the clinical implication of PRD in patients with mRCC to select better candidates in whom NIVO+IPI can be initiated as first-line therapy. METHODS: This multi-institutional retrospective cohort study used data collected between August 2015 and January 2023. In total, 120 patients with mRCC treated with NIVO+IPI were eligible. Associations between immune-related adverse events and progression-free survival, overall survival (OS), and objective response rate were analyzed. The relationship between other clinical factors and outcomes was also evaluated. RESULTS: The median observation period was 16 months (interquartile range, 5-27). The median age at NIVO+IPI initiation was 68 years in the male-dominant population (n = 86, 71.7%), and most patients had clear cell histology (n = 104, 86.7%). PRD was recorded in 26 (23.4%) of 111 investigated patients during NIVO+IPI therapy. Patients who experienced PRD showed worse OS (hazard ratio: 4.525, 95% confidence interval [CI]: 2.315-8.850, p < 0.001). Multivariable analysis showed that lymph node metastasis (LNM) (odds ratio: 4.274, 95% CI: 1.075-16.949, p = 0.039) was an independent risk factor for PRD. CONCLUSIONS: PRD was strongly correlated with worse survival rates. LNM was independently associated with PRD in patients with mRCC receiving NIVO+IPI as first-line therapy and might indicate that a candidate will not benefit from NIVO+IPI.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Male , Aged , Nivolumab/adverse effects , Ipilimumab/adverse effects , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/etiology , Retrospective Studies , Kidney Neoplasms/pathology , Antineoplastic Combined Chemotherapy Protocols/adverse effects
18.
Cancers (Basel) ; 15(7)2023 Mar 28.
Article in English | MEDLINE | ID: mdl-37046663

ABSTRACT

Upper urinary tract urothelial carcinoma (UTUC) after intravesical bacillus Calmette-Guerin (BCG) therapy is rare, and its incidence, clinical impact, and risk factors are not fully understood. To elucidate the clinical implications of UTUC after intravesical BCG therapy, this retrospective cohort study used data collected between January 2000 and December 2019. A total of 3226 patients diagnosed with non-muscle-invasive bladder cancer (NMIBC) and treated with intravesical BCG therapy were enrolled (JUOG-UC 1901). UTUC impact was evaluated by comparing intravesical recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) rates. The predictors of UTUC after BCG treatment were assessed. Of these patients, 2873 with a medical history that checked UTUC were analyzed. UTUC was detected in 175 patients (6.1%) during the follow-up period. Patients with UTUC had worse survival rates than those without UTUC. Multivariate analyses revealed that tumor multiplicity (odds ratio [OR], 1.681; 95% confidence interval [CI], 1.005-2.812; p = 0.048), Connaught strain (OR, 2.211; 95% CI, 1.380-3.543; p = 0.001), and intravesical recurrence (OR, 5.097; 95% CI, 3.225-8.056; p < 0.001) were associated with UTUC after BCG therapy. In conclusion, patients with subsequent UTUC had worse RFS, CSS, and OS than those without UTUC. Multiple bladder tumors, treatment for Connaught strain, and intravesical recurrence after BCG therapy may be predictive factors for subsequent UTUC diagnosis.

19.
Membranes (Basel) ; 13(1)2023 Jan 02.
Article in English | MEDLINE | ID: mdl-36676864

ABSTRACT

Polytetrafluoroethylene (PTFE) is the most widely used fluoropolymer that has various functionalities such as heat resistance, chemical resistance, abrasion resistance, and non-adhesiveness. However, PTFE is difficult to dye because of its high water repellency. In this study, the PTFE surface was modified by a combination of gold sputtering and surface fluorination to improve dyeability. X-ray photoelectron spectroscopy indicated that, compared with the untreated sample, the gold-sputtered and acid-washed surface of PTFE had a negligible number of C-F terminals. Furthermore, the intensity of the C-C peak increased drastically. The polar groups (C=O and C-Fx) increased after surface fluorination, which enhanced the electronegativity of the surface according to the zeta potential results. Dyeing tests with methylene blue basic dye showed that the dye staining intensity on the surface of fluorinated PTFE samples was superior to other samples. It is due to the increased surface roughness and the negatively charged surface of fluorinated PTFE samples. The modified PTFE substrates may find broad applicability for dyeing, hydrophilic membrane filters, and other adsorption needs.

20.
Hum Genome Var ; 9(1): 35, 2022 Sep 29.
Article in English | MEDLINE | ID: mdl-36175418

ABSTRACT

Biotin-responsive basal ganglia disease (BBGD) with SLC19A3 mutation was first reported in 1998, and over 30 mutations have been reported. We report a neonatal BBGD case with sudden-onset feeding difficulty and impaired consciousness. Encephalopathy resolved after the initiation of biotin and thiamine treatment. Genetic testing revealed a novel heterozygous mutation [c.384_387del, p.Tyr128fs];[c.265 A > C, p.Ser89Arg] in SLC19A3. Early treatment for BBGD is essential, especially with onset in the neonatal or early infancy period.

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