Prostate cancer antigen 3 (PCA3) is a prostate cancer-specific long noncoding RNA (lncRNA). Here, we report that lncRNA PCA3 plays a role in prostate cancer progression that is mediated by ...nucleoplasmic lamins. PCA3 interacts with the C-terminal region of lamina-associated polypeptide (LAP) 2α. The C-terminal region of LAP2α includes tumor suppressor protein retinoblastoma (pRb)- and lamin-binding domains, and it is necessary for the regulation and stabilization of the nucleoplasmic pool of lamin A. PCA3 inhibits the interaction of LAP2α with lamin A through binding with the C-terminus of LAP2α. The level of nucleoplasmic lamin A/C is increased by knockdown of PCA3. Together, the level of LAP2α within the nucleus is increased by PCA3 knockdown. In PCA3 knockdown cells, the levels of HP1γ, trimethylation of Lys9 on histone H3 (H3K9me3), and trimethylation of Lys36 on histone H3 (H3K36me3) are upregulated. In contrast, trimethylation of Lys4 on histone H3 (H3K4me3) is downregulated. We further demonstrate that activation of the p53 signaling pathway and cell cycle arrest are promoted in the absence of PCA3. These findings support a unique mechanism in which prostate cancer-specific lncRNA controls chromatin organization via regulation of the nucleoplasmic pool of lamins. This proposed mechanism suggests that cancer progression may be mediated by nuclear lamins.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
Population-based prostate-specific antigen (PSA) screening is effective for reducing prostate cancer (PCa)-related mortality rates. In this study, we assessed biopsy-proven maximum cancer ...core length (MCCL) and maximum cancer diameter on magnetic resonance imaging (MRI; MCDM) in prostate biopsy and multiparametric MRI (mp-MRI) by PCa detection.
Methods
We retrospectively assessed 214 male PCa patients and 187 PCa patients with Prostate Imaging Reporting and Data System version 2 (PI-RADS) category 3–5 lesions in pre-biopsy mp-MRI and targeted biopsy characteristics. The mean biopsy-proven MCCL and MCDM were compared among three PSA screening groups, namely the population-based PSA screening (PBS), opportunistic PSA screening (OPS), and symptomatic outpatient PSA examination (SOP) groups.
Results
The median age and PSA value of the 214 participants were 75 years and 7.9 ng/mL, respectively. In the PBS, OPS, and SOP groups, the median ages were 73, 76, and 76 years, respectively (
p
= 0.046); PSA values were 7.2, 9.5, and 11.5 ng/mL, respectively (
p
< 0.001); and biopsy-proven MCCL and MCDM were significantly increased to 7, 10, and 14 mm (
p
< 0.001) and to 11, 15, and 17 mm (
p
< 0.001), respectively. In the 187 PCa patients with PI-RADS category 3–5 lesions on mp-MRI, MCDM were 11, 14, and 17 mm (
p
< 0.001), respectively.
Conclusions
The biopsy-proven MCCL and MCDM were significantly smaller in the PBS and OPS groups than in the SOP group, which suggests that PSA screening detected PCa earlier than in symptomatic patients. PSA screening with MRI could objectively lead to earlier diagnosis based on tumor size.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
IMA901 is the first therapeutic vaccine for renal cell cancer (RCC). It contains multiple tumor‐associated peptides (TUMAPs) that are naturally present in human cancers.
Methods
In a phase ...I/II study, we treated a total of 10 Japanese patients with advanced RCC who were human leukocyte antigen A (HLA‐A)*02 +. Vaccination involved i.d. injection of GM‐CSF (75 μg), followed within 15–30 min by i.d. injection of IMA901 (containing 413 μg of each peptide). No treatment with either anticancer agents or immunosuppressants was allowed within 4 weeks before entering the trial. Patients were scheduled to receive 7 vaccinations during the first 5 weeks of treatment (induction period), followed by 10 further vaccinations at 3‐week intervals for up to 30 weeks (maintenance period). The primary endpoints were safety and tolerability, while the secondary endpoints were PFS, OS, and immunogenicity.
Results
There were no treatment‐related serious adverse events or deaths during the study period. When the response was assessed after 4 months, 10% of patients showed a partial response, 80% had stable disease, and 10% had progressive disease. Among patients in whom the T‐cell response was analyzed, five patients showed a vaccine‐induced T‐cell response against at least one HLA class I‐restricted TUMAP and two patients had T‐cell responses to multiple TUMAPs. PFS was 5.5 months and OS was 18 months.
Conclusions
This study demonstrated the safety and tolerability of IMA901 vaccine in Japanese RCC patients, and also showed that vaccination elicited an immune response.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
37.
New year's greetings Ukimura, Osamu
International journal of urology,
January 2024, 2024-Jan, 2024-01-00, 20240101, Volume:
31, Issue:
1
Journal Article
Peer reviewed
Open access
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Purpose We present a novel concept of zero ischemia anatomical robotic and laparoscopic partial nephrectomy. Materials and Methods Our technique primarily involves anatomical vascular microdissection ...and preemptive control of tumor specific, tertiary or higher order renal arterial branch(es) using neurosurgical aneurysm micro-bulldog clamps. In 58 consecutive patients the majority (70%) had anatomically complex tumors including central (67%), hilar (26%), completely intrarenal (23%), pT1b (18%) and solitary kidney (7%). Data were prospectively collected and analyzed from an institutional review board approved database. Results Of 58 cases undergoing zero ischemia robotic (15) or laparoscopic (43) partial nephrectomy, 57 (98%) were completed without hilar clamping. Mean tumor size was 3.2 cm, mean ± SD R.E.N.A.L. score 7.0 ± 1.9, C-index 2.9 ± 2.4, operative time 4.4 hours, blood loss 206 cc and hospital stay 3.9 days. There were no intraoperative complications. Postoperative complications (22.8%) were low grade (Clavien grade 1 to 2) in 19.3% and high grade (Clavien grade 3 to 5) in 3.5%. All patients had negative cancer surgical margins (100%). Mean absolute and percent change in preoperative vs 4-month postoperative serum creatinine (0.2 mg/dl, 18%), estimated glomerular filtration rate (−11.4 ml/minute/1.73 m2 , 13%), and ipsilateral kidney function on radionuclide scanning at 6 months (−10%) correlated with mean percent kidney excised intraoperatively (18%). Although 21% of patients received a perioperative blood transfusion, no patient had acute or delayed renal hemorrhage, or lost a kidney. Conclusions The concept of zero ischemia robotic and laparoscopic partial nephrectomy is presented. This anatomical vascular microdissection of the artery first and then tumor allows even complex tumors to be excised without hilar clamping. Global surgical renal ischemia is unnecessary for the majority of patients undergoing robotic and laparoscopic partial nephrectomy at our institution.
The combination of T2-weighted MRI with functional MRI, including contrast-enhanced MRI, diffusion-weighted imaging and magnetic resonance spectroscopy, has been recognized as the most promising ...diagnostic modality for the detection and staging of localized prostate cancer. In spite of the relatively low predictive value of the transrectal ultrasonography (US) image alone, transrectal US-guided prostate biopsy is currently the most clinically used, gold standard technique to confirm pathological prostate cancer. A possible way of improving the precision of prostate biopsy is to use computer-aided analysis, the fusion of the US image with MRI, or by introducing contrast-enhanced US, elastography and/or 3D US to be coupled with computer-assistance or robotic needle placement. Computer-aided surgical navigation systems with image-fusion or image-overlaying capability, integrated with real-time organ tracking systems and/or robotic systems for feedback on the 3D spatial positions of the surgical targets and instruments, can provide attractive opportunities to improve the digitally-coordinated precision of minimally invasive urology, along with predictive ability to guide toward ideal surgical outcomes.
The androgen receptor (AR) promotes growth of prostate cancer cells by controlling the expression of target genes. This study showed that MRG domain binding protein (MRGBP) accelerated AR-mediated ...transactivation. We first showed that MRGBP promoted growth of AR-positive prostate cancer cells. MRGBP increased the expression of certain AR target genes, including KLK3 and TMPRSS2, and it associated with AR binding regions of these genes during androgen treatment. Furthermore, MRGBP interacted with MRG15 and TIP60 in prostate cancer cells. Androgen-stimulated AR enhanced histone H3K4me1 or H3K4me3 levels at AR binding regions. MRGBP was recruited to active gene regions through its binding with H3K4me1/3 by MRG15. Then, MRGBP promoted recruitment of TIP60 and acetylation of histone variant H2A.Z at the location of AR binding. Accordingly, AR occupancy of the AR binding regions was increased by MRGBP. Together, these results suggest that MRGBP promotes activation of AR-associated enhancer and promoter regions through an epigenetic mechanism.
•Growth of prostate cancer cells was promoted by MRGBP.•MRGBP increased the expression levels of AR target genes in prostate cancer cells.•MRGBP was recruited to AR binding regions by associating with histone H3K4me1/3 upon androgen stimulation.•MRGBP promoted both the recruitment of TIP60 and the acetylation of histone H2A.Z at AR binding regions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
