Radioligand Therapy With 177 Lu-PSMA-I&T in Patients With Metastatic Prostate Cancer : Oncological Outcomes and Toxicity Profile.

INTRODUCTION: This study aimed to investigate the oncological outcomes and toxicity profile of 177 Lu-PSMA-I&T radioligand therapy (RLT) in patients with metastatic castration-resistant prostate cancer (mCRPC), as well as our initial experience in metastatic hormone-sensitive prostate cancer (mHSPC). PATIENTS AND METHODS: A total of 38 consecutive patients with metastatic prostate cancer (33 mCRPC and 5 mHSPC) received 177 Lu-PSMA-I&T RLT, with a median of 2 cycles per patient (range, 1-7). Response to RLT was evaluated based on prostate-specific antigen (PSA) changes and imaging response. Clinical progression-free survival and overall survival were used to report oncological outcomes. Toxicity was assessed using the Common Toxicity Criteria for Adverse Events criteria. RESULTS: In mCRPC, 22 (69%), 18 (56%), and 11 (34%) patients achieved any PSA decline, PSA response of ≥30%, and PSA response of ≥50%, respectively. The clinical progression-free survival and overall survival after the first cycle of RLT were 6.3 and 21.4 months, respectively. In mHSPC, 177 Lu-PSMA-I&T RLT resulted in excellent PSA response (93.0%-99.9%) in all cases. Clinical progression and cancer-related mortality occurred in only 1 case. Toxicity profile was favorable in both mHSPC and mCRPC. CONCLUSIONS: 177 Lu-PSMA-I&T RLT demonstrated favorable PSA response (≥30%) in over half of the patients with mCRPC and excellent PSA response in all patients with mHSPC. Toxicity profile was favorable in both mHSPC and mCRPC settings. Further studies are needed to evaluate the role of 177 Lu-PSMA-I&T RLT in the management of metastatic prostate cancer.

Peripheral blood B cell subset ratios and expression levels of B cell-associated genes are altered in benign multiple sclerosis.

The interplay between the immune system, sleep dysfunction and cognitive impairment participates in the progression of disability in multiple sclerosis (MS). Our aim was to identify molecular pathways and B cell associated with separate components of MS disability. Benign MS, non-benign MS patients and healthy controls were recruited. Patients underwent polysomnography and cognitive studies. Microarray and bioinformatics analysis performed using peripheral blood mononuclear cell samples identified B cell-associated genes with the most significantly altered expression. Expression levels of these genes were validated by real-time PCR and peripheral blood cell subsets were examined by flow cytometry. Putative correlations among clinical and laboratory parameters were investigated by correlation network analysis. Sleep and cognitive functions were equally impaired in BMS and NBMS. BMS patients showed significantly reduced memory B cell and increased regulatory B cell percentages than NBMS patients. Among genes that were selected by bioinformatics, levels of BLK, BLNK, BANK1, FCRL2, TGFB1 and KCNS3 genes were significantly different among study subgroups. Correlation network analysis showed associations among physical-cognitive disability and sleep dysfunction measures of MS versus expression levels of selected genes. BMS and NBMS differ by physical disability but not cognitive and sleep dysfunction. Different components of disability in MS are associated with peripheral blood B cell ratios and B cell related gene expression levels. Thus, it is likely that altered B cell functions participate in the progression of disability in MS.

Cytokine-chemokine and cognitive profile of multiple sclerosis patients with predominant optic nerve and spinal cord involvement.

Context/Objective: Clinical disease activity in multiple sclerosis (MS) may manifest as predominant involvement of optic nerves and spinal cord, as exemplified by opticospinal multiple sclerosis (OSMS) often encountered in Asian countries. Our aim was to compare the clinical features, neuropsychological profile and cytokine/chemokine levels of patients with conventional MS (CMS) and MS presenting predominantly with spinal cord and optic nerve attacks (MS-SCON).Design: Cross-sectional study.Setting: MS Outpatient Clinic.Participants: Fourteen MS-SCON patients, 20 CMS patients without myelitis and optic neuritis attacks and 21 healthy individuals.Outcome measures: IL-8, IL-10, IFN-γ, IL-17 and TNF-α levels were measured by multiplex assay and CXCL2 and CXCL5 levels were measured by ELISA. A panel of neuropsychological tests, Beck depression inventory, 9-hole peg and timed 25-foot walk tests were employed.Results: CMS and MS-SCON patients showed similar clinical features. Both CMS and MS-SCON patients displayed reduced IL-8 and CXCL2 and increased TNF-α levels, while IL-10 and CXCL5 levels were identical among all groups.Conclusion: Neuropsychological and motor function test performances of CMS and MS-SCON patients were highly comparable. CMS and MS-SCON present with similar clinical, neuropsychological and immunological features. Therefore, optic nerve and spinal cord-dominant form of MS does not necessarily establish a distinct entity in our region. Cognitive networks of the central nervous system may be damaged during the disease course of MS, despite the absence of cerebral or cerebellar clinical attacks.

Determination of thyroglobulin levels by radioimmunoassay method in anti thyroglobulin positive differentiated thyroid patients: One center clinical experience.

It is very crucial to determine Tg accurately and precisely in thyroid cancer cases. Although there are many studies on the detection of Tg in thyroid cases in the literature, there are no sufficient clinical studies examining many cases with different features by using RIA methodology. Here, a radiometric and chromatographic method has been studied for the first time to eliminate the interference from anti-Tg positive patients. In this paper, radioimmunoassay (RIA) and immunoradiometric (IRMA) techniques were used for the analysis of 302 sera collected from patients for Tg and TgAb quantification. By the RIA technique, a reliable result was obtained by calculating the real Tg value quantitatively in 41 patients showing TgAb positivity out of 208 patients. Our findings show that the RIA assay is the most suitable approach for detection of changeable (low or undetectable) Tg value and metastases detected by post-therapeutic imaging in early-stage DTC cases showing preoperative and postoperative TgAb positivity. The new immunoradiometric method allows the real (%) Tg value to be reached in a part of TgAb-positive DTC. Even if TgAb positive in the metastatic and nonmetastatic DTC patient group. This allows the accurate clinical follow-up of patients.

Serum levels of inflammasome pathway factors in clinically isolated syndrome and multiple sclerosis patients: a pilot study.

Pathogenic roles of nuclear factor κB (NF-κB) pathway and NLRP3 inflammasome complex factors are involved in multiple sclerosis (MS) development. Activation of the NF-κB, NLRP3, and caspase-1 cascade results in production of proinflammatory cytokines that lead to stimulation of macrophages, lymphocytes, and glial cells. Although increased levels of inflammasome complex factors are observed in MS, contribution of inflammasome pathway to conversion from clinically isolated syndrome (CIS) to relapsing remitting MS (RRMS) has been scarcely investigated. To examine predictive value of inflammasome factors in CIS-MS conversion, levels of NLRP3, caspase-1, and NFκB are measured by ELISA in sera of age-gender matched CIS (n = 18; 8 converting, 10 non-converting) and RRMS (n = 23) patients. CIS and RRMS patients have comparable serum levels of NLRP3, caspase-1, and NFκB. Similarly, no statistically significant difference can be found among converting and non-converting CIS patients by means of inflammasome complex factor levels. Inflammasome factors are presumably overexpressed at early stages of MS. Therefore, they are unlikely to be used as biomarkers to predict CIS-MS conversion.

Serum orexin-A levels are associated with disease progression and motor impairment in multiple sclerosis.

OBJECTIVE: Diencephalon is frequently affected in multiple sclerosis (MS), and lesions of this region are associated with increased disability. Orexin-A and melatonin, two foremost mediators of diencephalon, modulate cognitive and motor functions through several pathways including the brain-derived neurotrophic factor (BDNF)-cAMP response element-binding protein (CREB) signaling pathway. In this pilot study, our aim was to investigate the prognostic value of these factors in progression of cognitive and physical disability. METHODS: Levels of BDNF, melatonin, CREB, and orexin-A were determined by ELISA in sera of 25 relapsing remitting MS (RRMS) patients, 15 secondary progressive MS (SPMS) patients, and 20 healthy controls. Cognitive and motor functions were assessed by a neuropsychological test battery, timed 25-ft walk (T25-FW) and 9-hole peg (9-HP) tests. RESULTS: MS patients had significantly lower serum levels of orexin-A and BDNF than healthy controls, and SPMS patients had significantly lower levels of melatonin and orexin-A than RRMS patients. Serum orexin-A levels were negatively correlated with 9-HP, T25-FW test scores, and progression index in RRMS patients. BDNF, CREB, and melatonin levels did not show any significant correlation with clinical features including EDSS and cognitive/motor performance of the patients. CONCLUSION: Our results suggest that orexin-A levels are decreased in parallel to disease progression and motor system deterioration in the earlier stages of the disease. Thus, orexin-A might be used as a potential biomarker of physical disability.