Kobe Central Hospital

Weerda

To investigate factors associated with symptomatic urinary tract infection (sUTI) in persons with chronic spinal cord lesion (SCL) who were using single-use catheters for intermittent self-catheterization (ISC). Among respondents to an internet survey on the burden of illness on persons with SCL who were considered to be able to perform ISC, 111 persons using single-use catheters were included to examine factors associated with self-reported sUTI by univariate as well as multivariable analysis. The incidence of sUTI was significantly higher in males than in females (56.9% vs. 31.6%, p = .011), persons with stocks of antibiotics than those without it (82.9% vs. 28.6%, p < .011), and persons with more frequent bleeding during catheterization than those with less frequent bleeding (100% vs. 46.5%, p = .036). The incidence did not significantly differ between respective groups when various variables were evaluated by other characteristics of the participants, adherence to ISC procedures, and complications. On multivariable analysis, male gender and stocks of antibiotics were significant independent factors for sUTI. Male gender and stocks of antibiotics were associated with sUTI in persons with SCL who were performing ISC with single-use catheters.

&lt;div&gt;Abstract&lt;p&gt;Rhabdoid tumor is an aggressive, early childhood tumor. Biallelic inactivation of the SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (&lt;i&gt;SMARCB1&lt;/i&gt;)/integrase interactor 1 (&lt;i&gt;INI1&lt;/i&gt;) gene is the only common genetic feature in rhabdoid tumors. Loss of &lt;i&gt;SMARCB1&lt;/i&gt; function results in downregulation of several tumor suppressor genes including &lt;i&gt;p16, p21&lt;/i&gt;, and &lt;i&gt;NOXA&lt;/i&gt;. The novel histone deacetylase inhibitor, OBP-801, induces &lt;i&gt;p21&lt;/i&gt; and has shown efficacy against various cancers. In our study, OBP-801 strongly inhibited the cell growth of all rhabdoid tumor cell lines in WST-8 assay. However, Western blotting and cell-cycle analysis revealed that OBP-801 did not activate the P21-RB pathway in some cell lines. &lt;i&gt;p21&lt;/i&gt; knockout indicated that &lt;i&gt;p21&lt;/i&gt; did not dominate the OBP-801 antitumor effect in rhabdoid tumor cell lines. We discovered that OBP-801 induced &lt;i&gt;NOXA&lt;/i&gt; expression and caspase-dependent apoptosis in rhabdoid tumor cell lines independent of TP53. Chromatin immunoprecipitation assay showed that OBP-801 acetylated histone proteins and recruited RNA polymerase II to the transcription start site (TSS) of the &lt;i&gt;NOXA&lt;/i&gt; promotor. Moreover, OBP-801 recruited BRG1 and BAF155, which are members of the SWI/SNF complex, to the TSS of the &lt;i&gt;NOXA&lt;/i&gt; promotor. These results suggest that OBP-801 epigenetically releases the silencing of &lt;i&gt;NOXA&lt;/i&gt; and induces apoptosis in rhabdoid tumors. OBP-801 strongly inhibited tumor growth in human rhabdoid tumor xenograft mouse models &lt;i&gt;in vivo&lt;/i&gt;. Terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling and cleaved caspase-3 were stained in tumors treated with OBP-801. In conclusion, OBP-801 induces apoptosis in rhabdoid tumor cells by epigenetically releasing the silencing of &lt;i&gt;NOXA&lt;/i&gt;, which is a key mediator of rhabdoid tumor apoptosis. The epigenetic approach for &lt;i&gt;NOXA&lt;/i&gt; silencing with OBP-801 is promising for rhabdoid tumor treatment.&lt;/p&gt;&lt;/div&gt;

Novel therapeutic drugs have dramatically improved the overall survival of patients with multiple myeloma. We sought to identify the characteristics of patients likely to exhibit a durable response to one such drug, elotuzumab, by analyzing a real-world database in Japan. We analyzed 179 patients who underwent 201 elotuzumab treatments. The median time to next treatment (TTNT) with the 95% confidence interval was 6.29 months (5.18–9.20) in this cohort. Univariate analysis showed that patients with any of the following had longer TTNT: no high risk cytogenic abnormalities, more white blood cells, more lymphocytes, non-deviated κ/λ ratio, lower β2 microglobulin levels (B2MG), fewer prior drug regimens, no prior daratumumab use and better response after elotuzumab treatment. A multivariate analysis showed that TTNT was longer in patients with more lymphocytes (≥ 1400/μL), non-deviated κ/λ ratio (0.1–10), lower B2MG (< 5.5 mg/L) and no prior daratumumab use. We proposed a simple scoring system to predict the durability of the elotuzumab treatment effect by classifying the patients into three categories based on their lymphocyte counts (0 points for ≥ 1400/μL and 1 point for < 1400/μL) and κ/λ ratio (0 points for 0.1–10 and 1 point for < 0.1 or ≥ 10) or B2MG (0 points for < 5.5 mg/L and 1 point for ≥ 5.5 mg/L). The patients with a score of 0 showed significantly longer TTNT (p < 0.001) and better survival (p < 0.001) compared to those with a score of 1 or 2. Prospective cohort studies of elotuzumab treatment may be needed to validate the usefulness of our new scoring system.

Introduction: The differences in biological characteristics among different genotypes of classical EGFR mutations have not been clarified. This study aimed to clarify the clinical and biological differences between L858R and 19 deletion in NSCLC. Methods: We analyzed a cohort of 191 consecutive cases of surgically resected NSCLC harboring EGFR driver mutations (L858R or 19 deletion) in which curative resection was performed in Aichi Cancer Center Hospital, Nagoya, Japan, from January 2006 to September 2021 and in which recurrence subsequently developed. We also subjected 61 surgically resected NSCLC specimens harboring EGFR driver mutations (L858R or 19 deletion) to an RNA sequencing analysis. Results: In patients with stage I disease, the median time to recurrence did not differ to a statistically significant extent between the types of EGFR mutations; however, among those with stage II and III disease, the median time to recurrence in patients with the L858R genotype tended to be shorter in comparison to those with 19 deletion (log-rank test, p = 0.47 and 0.46, respectively). In comparison to 19 deletion tumors, L858R tumors had higher cytological malignancy (e.g., mitotic ability) and showed stronger immunogenicity. Conclusion: L858R and 19 deletion tumors are likely to have a slight difference in the time to recurrence. They suggest that even in EGFR driver tumors, which are treated as the same disease category, the biological characteristics of the tumors are different, which may leave room for innovations in postoperative treatment and treatment at recurrence.

The Archer FusionPlex platform is widely used for comprehensive fusion-gene detection in cancer tissues. This platform separately displays results for strong-evidence and weak-evidence fusion candidates (WEFCs). Distinctive fusion patterns are frequently found in the weak-evidence category and information about the patterns is clinically essential. We describe the type and frequency of WEFCs observed using the FusionPlex Sarcoma Panel (S Panel) and the FusionPlex ALK, RET, and ROS1 ver2 Panel (ARR Panel). A total of 97 specimens were examined and 620 candidates were detected and categorized as WEFCs. A median of five WEFCs were detected per sample. In the S Panel group, there were 13 WEFCs with a frequency of more than 1%. In the ARR Panel group, a total of 16 WEFCs were detected with a frequency of more than 1%. Specific WEFCs were detected according to the panel selected.

The Japan Study Group for Cell Therapy and Transplantation (JSCT) organized a phase II study to evaluate the efficacy and safety of a treatment protocol (JSCT-MM12) for multiple myeloma (MM) patients who were previously untreated and transplantation-eligible. Since bortezomib-based therapy is known to be effective for MM, the protocol is intensified more than the previous protocol (JSCT-MM10) and comprised the subsequent treatments: bortezomib + cyclophosphamide + dexamethasone (VCD) induction; bortezomib + high-dose-melphalan (B-HDM) conditioning with autologous stem cell transplantation (ASCT); bortezomib + thalidomide + dexamethasone (VTD) consolidation; and lenalidomide (LEN) maintenance. Sixty-four symptomatic patients aged between 20 and 65years were enrolled for treatment and received three cycles of VCD, followed by cyclophosphamide administration for autologous stem cell harvest and B-HDM/ASCT, and subsequently two cycles of VTD, after that LEN for 1year. Complete response (CR)/stringent CR (sCR) rates for induction, ASCT, consolidation, and maintenance therapies were 20, 39, 52, and 56%, respectively. The grade 3/4 toxicities (≥ 10%) with VCD treatment included neutropenia (27%), anemia (19%), and thrombocytopenia (11%). There was no treatment-related mortality. After median follow-up of 41months, estimated 3-year progression-free survival (PFS) and overall survival (OS) rates were 64% and 88%, respectively. The high-risk group revealed lower CR/sCR, PFS, and OS than the standard-risk group. The study revealed that the treatment protocol consisting of VCD induction, B-HDM/ASCT followed by VTD consolidation, and LEN maintenance could produce highly beneficial responses and favorable tolerability in newly diagnosed MM. However, future study is required for improving treatment in the high-risk group.