Dysplastic aberrant left subclavian artery originating from a thoracic intersegmental artery associated with a right aortic arch.

PURPOSE: A right aortic arch (RAA) is a rare vascular anomaly that often coexists with an aberrant left subclavian artery (ALSA). Due to the rarity of RAA, the development of an ALSA is not well understood. METHOD: We describe a case in which a 58-year-old man who was scheduled to undergo posterior decompression and fusion surgery for thoracic ossification of the posterior longitudinal ligament from Th1 to Th3 was found to have a RAA and an ALSA. RESULTS: Preoperative computed tomography angiography demonstrated a RAA and an ALSA. The ALSA was extremely tortuous and ran in the paraspinal muscles behind the thoracic laminae, which meant it was in the surgical field. The ALSA arose from the descending aorta and bifurcated into the left segmental arteries of Th1 and Th2, and also bifurcated into the left vertebral artery, which had a normal subsequent course. The dysplastic ALSA was considered to have developed from the thoracic intersegmental artery. Based on preoperative examination findings, we performed spinal surgery without vessel injury. CONCLUSION: We report a rare case of a dysplastic ALSA that developed from the thoracic intersegmental artery with a RAA. The knowledge of this anomaly provides safety in spinal surgery of the cervicothoracic junction.

Posterior inferior cerebellar artery originating from the posterior meningeal artery mimicking dural arteriovenous fistula.

PURPOSE: Many variations in the origin of the posterior inferior cerebellar artery (PICA) have been reported. To our knowledge, only one case of a PICA originating from the posterior meningeal artery (PMA) has been reported. METHODS: We describe a case with a PICA that was supplied retrograde from the distal segment of the PMA, mimicking a dural arteriovenous fistula on magnetic resonance angiography (MRA). RESULTS: A 31-year-old man was admitted to our hospital with a sudden occipital headache and nausea. MRA showed a hyperplastic left PMA, continuing to an abnormal vessel that was suspicious for venous drainage. Digital subtraction angiography revealed the left PMA originated from the extradural segment of the vertebral artery and then connected to the left PICA near the torcula. The cortical segment of the PICA flowed retrograde, which appeared as venous reflux on MRA. A second PICA originated from the extradural segment of the left vertebral artery and perfused the tonsillomedullary and televelotonsillar segment of the left PICA territory. CONCLUSION: We present an anatomical variant of the PICA mimicking a dural arteriovenous fistula. Digital subtraction angiography is useful for diagnosis of the cortical segment of the PICA flowing retrograde from the distal segment of the PMA because signal intensity in MRA of retrograde flow tends to decrease and diagnosis may be difficult. During endovascular treatment and open surgery, we should note that ischemic complications may occur due to the potential anastomosing channels between cerebral and dural arteries.

Ternary Amorphous Solid Dispersions Containing a High-Viscosity Polymer and Mesoporous Silica Enhance Dissolution Performance†.

The aim of this study was to evaluate the benefits of a ternary amorphous solid dispersion (ASD) that was designed as an immediate-release tablet with a high drug load (e.g., 40% w/w) to produce heightened maintenance of drug supersaturation during dissolution testing, which will be henceforth referred to as the "maintenance ability". Ternary ASD granules were produced by hot melt extrusion (HME) and were comprised of itraconazole (ITZ) 50%, hypromellose (HPMC) 20%, and mesoporous silica (XDP) 30%, where amorphous ITZ incorporated into HPMC was efficiently absorbed in XDP pores. The ternary ASD granules containing a high-viscosity HPMC (AF4M) produced a significantly heightened maintenance ability of drug supersaturation in neutral pH dissolution media in which crystalline ITZ solubility is below 1 µg/mL. The final tablet formulation contained 80% w/w of the ASD granules (40% w/w ITZ), had an acceptable size, and exhibited both sufficient tablet hardness and disintegration. The dissolution behavior of the ternary ASD tablet exhibited a supersaturation maintenance ability similar to that of the ASD granules. Under neutral conditions, the ternary ASD tablet showed immediate and higher ITZ release compared with the binary ASD tablets, and this phenomenon could be explained by the difference in ITZ/AF4M particle size in the tablet. In high-resolution scanning electron microscopy (SEM), it was observed that ITZ and AF4M in the ternary formulation could easily form nano-sized particles (<1 µm) during the absorption process into/onto XDP pores prepared by HME, which contributed to the immediate ITZ release from the ternary ASD tablet under neutral pH conditions. Therefore, the ternary ASD containing high-viscosity HPMC and mesoporous silica prepared by HME made it possible to design a high ASD content, small-size tablet with an ideal dissolution profile in biorelevant media, and we expect that this technology can be applied for continuous HME ASD manufacturing.

[What are the Indications and Points of Anterior Cervical Decompression Surgery?]

Anterior cervical foraminotomy is a motion-preserving and precise decompressing surgery with minimal bone removal. As preserving the motion segment and maximizing decompression are contradictory concepts, proficiency is needed to balance these requirements. Anatomical knowledge and good intraoperative orientation are essential to reach the nerve roots accurately in a narrow surgical field.

[Clinical Significance of the Curative Effect after Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer-Correlation to Prognosis].

We investigated factors related to the recurrence and prognosis of patients with triple-negative breast cancer (TNBC)after neoadjuvant chemotherapy(NAC). Of the 545 patients who underwent surgery after NAC between January 2013 and December 2016, 131 patients had TNBC. An analysis of each TNBC case indicated that the presence or absence of clinical lymph node metastasis(cN)before treatment might be a predictive factor of prognosis. There were 57(43.5%)pathological complete response(pCR)(ypT0 or ypTis/N0)cases after NAC. Overall survival(OS)and disease free survival(DFS) were significantly better in pCR cases than in non-pCR cases. However, recurrence was observed in 8 of 57(14%)pCR cases and 29 of 74(39%)non-pCR cases. The factors defining DFS from the univariate analysis of the non-pCR group were cN, ypT, ypN, and vascular invasion. The multivariate analysis of these factors suggested that residual cN and vascular invasion might be independent factors predicting DFS. Residual vascular invasion was found to predict OS, and was considered to be a poor prognostic factor.

Motor coordination during body rotation while standing in healthy participants.

[Purpose] To describe the nature of multi-joint motor coordination during body rotation while in the standing position. [Participants and Methods] The participants were 22 healthy adults with no visual problems or history of diseases that could compromise their ability to execute body rotation. The position facing forward in an upright standing position was defined as 0°, and targets were placed at the following five points on concentric circles: 30°, 60°, 90°, 120°, and 150°. The participants always turned to the right. A three-dimensional motion analyzer consisting of six infrared cameras was used to measure the spatial coordinates of the infrared reflective markers. [Results] A main effect was found for all body segments. For all the target angles, the start of movement was approximately equal, and the angular change of the craniocervical joint was the largest. A nonlinear relationship was observed between the craniocervical and thoracolumbar joints for all target angles. However, a linear relationship was found between the thoracolumbar and pelvic joints. [Conclusion] The results of this study demonstrate that various regions such as the craniocervical and thoracolumbar junctions and the pelvis coordinate during such move to achieve optimal locomotive patterns.

Sensitivity and specificity of mammography and adjunctive ultrasonography to screen for breast cancer in the Japan Strategic Anti-cancer Randomized Trial (J-START): a randomised controlled trial.

BACKGROUND: Mammography is the only proven method for breast cancer screening that reduces mortality, although it is inaccurate in young women or women with dense breasts. We investigated the efficacy of adjunctive ultrasonography. METHODS: Between July, 2007, and March, 2011, we enrolled asymptomatic women aged 40-49 years at 42 study sites in 23 prefectures into the Japan Strategic Anti-cancer Randomized Trial (J-START). Eligible women had no history of any cancer in the previous 5 years and were expected to live for more than 5 years. Randomisation was done centrally by the Japan Clinical Research Support Unit. Participants were randomly assigned in 1:1 ratio to undergo mammography and ultrasonography (intervention group) or mammography alone (control group) twice in 2 years. The primary outcome was sensitivity, specificity, cancer detection rate, and stage distribution at the first round of screening. Analysis was by intention to treat. This study is registered, number UMIN000000757. FINDINGS: Of 72,998 women enrolled, 36,859 were assigned to the intervention group and 36,139 to the control group. Sensitivity was significantly higher in the intervention group than in the control group (91·1%, 95% CI 87·2-95·0 vs 77·0%, 70·3-83·7; p=0·0004), whereas specificity was significantly lower (87·7%, 87·3-88·0 vs 91·4%, 91·1-91·7; p<0·0001). More cancers were detected in the intervention group than in the control group (184 [0·50%] vs 117 [0·32%], p=0·0003) and were more frequently stage 0 and I (144 [71·3%] vs 79 [52·0%], p=0·0194). 18 (0·05%) interval cancers were detected in the intervention group compared with 35 (0·10%) in the control group (p=0·034). INTERPRETATION: Adjunctive ultrasonography increases sensitivity and detection rate of early cancers. FUNDING: Ministry of Health, Labour and Welfare of Japan.

A randomized controlled trial to verify the efficacy of the use of ultrasonography in breast cancer screening aged 40-49 (J-START): 76 196 women registered.

OBJECTIVE: The objective of the Japan Strategic Anti-cancer Randomized Trial was to verify the efficacy of the use of ultrasonography in breast cancer screening among women aged 40-49 years. The purpose of this paper was to report the design and recruitment result of this study. METHODS: In this study of women in their 40s, the participants were divided into two groups, one of which (the intervention group) was subjected to mammography and ultrasonography (using a standardized ultrasonography examination), while the other (the control group) was examined with mammography, in a randomized controlled trial, with the objective of verifying the accuracy and efficacy of examinations by comparing the two groups. RESULTS: The cumulative total number of participants registered in the study was 76 196 (38 313 in the intervention group and 37 883 in the control group). 71.0% of participants registered to the study were under individual randomized controlled trial, 25.0% were under cluster randomized controlled trial and 3.9% were under non-randomized controlled group. The study was designed so that participants registered at their first examination underwent examinations by the same method for the subsequent two years. 74.1% of participants scheduled for a second examination had undertaken it, while information regarding the presence of interval cancer had been obtained from a further 20.6% using a questionnaire. At July 2013, the status of 5.3% of all participants was unclear. CONCLUSIONS: It was the first large-scale randomized controlled trial carried out in Japan. The scheduled second examinations were completed at the end of fiscal 2012. Once the proportion of participants whose status is unclear has fallen to ≤5%, the authors plan to collate the data relating to the primary end points, and publish the results.

Percutaneous ultrasound-guided cryoablation for early-stage primary breast cancer: a follow-up study in Japan.

BACKGROUND: Ultrasound-guided percutaneous cryoablation (PCA) for early-stage breast cancer (ESBC) can be performed under local anesthesia in an outpatient clinic. This study continues a pilot stage to examine local control, safety, patient quality of life (QoL), satisfaction and cosmetic outcomes of cryoablation for ESBC. METHODS: PCA was performed under local anesthesia for patients with primary ESBC, followed by radiation and endocrine therapies. Oncologic outcomes were examined by imaging (mammography, ultrasound, MRI) at baseline and 1, 6, 12, 24, 36, and 60 months post-cryoablation. EQ-VAS, EQ-5D-5L, subjective satisfaction and Moiré topography were used to measure health-related QoL outcomes. RESULTS: Eighteen patients, mean aged 59.0 ± 9.0 years, mean tumor size 9.8 ± 2.3 mm, ER + , PR + (17/18), HER2-, Ki67 < 20% (15/18), underwent PCA and were followed for a mean of 44.3 months. No serious adverse events were reported, and no patients had local recurrence or distant metastasis in the 5-year follow-up. Cosmetic outcomes, satisfaction level, and QoL all improved post-cryoablation. Five-year average reduction rates of the cryolesion long, short, and depth diameters, on US, were 61.3%, 42.3%, and 22.8%, respectively, compared to the 86.2% volume reduction rate on MRI. The correlation coefficient between MRI and US measurement criteria was highest for the long diameter. During follow-up, calcification of the treated area was observed in 13/18 cases. CONCLUSION: Cryoablation for ESBC is an effective and safe procedure with excellent cosmetic outcomes and improved QoL. This study contributes to the growing evidence supporting cryoablation as a potential standard treatment for ESBC, given compliance to pre-defined patient selection criteria.

Comparison of neoadjuvant chemohormonal therapy vs. extended pelvic lymph-node dissection in high-risk prostate cancer treated with robot-assisted radical prostatectomy.

We compared the impact of treatment strategies on postoperative complications and prognosis between robot-assisted radical prostatectomy (RARP) plus extended pelvic lymph-node dissection (ePLND) and RARP plus neoadjuvant chemohormonal therapy (NCHT) without ePLND. We retrospectively evaluated 452 patients with high-risk prostate cancer (defined as any one of prostate-specific antigen ≥ 20 ng/mL, Gleason score 8-10, or cT2c-3) who were treated with RARP between January 2012 and February 2021. The patients were divided into two groups: RARP with ePLND (ePLND group) and NCHT plus RARP without ePLND (NCHT group). We compared the complication rate (Clavien-Dindo classification), biochemical recurrence-free survival, and castration-resistant prostate cancer (CRPC)-free survival between the groups. We performed multivariable Cox regression analysis using inverse probability weighting (IPTW) methods to assess the impact of the different treatments on prognosis. There were 150 and 302 patients in the ePLND and NCHT groups, respectively. The postoperative complication rate was significantly higher in the ePLND group than in the NCHT group (P < 0.001). IPTW-adjusted biochemical recurrence-free survival and CRPC-free survival were significantly higher in the NCHT group than in the ePLND group (hazard ratio [HR] 0.29, P < 0.001, and HR 0.29, P = 0.010, respectively). NCHT plus RARP without ePLND may reduce the risk of postoperative complications compared with ePLND during RARP. The impact of treatment strategies on oncological outcomes needs further studies.

[SHORT-TERM SURGICAL AND FUNCTIONAL OUTCOMES AFTER ROBOT-ASSISTED SACROCOLPOPEXY IN A SINGLE INSTITUTION].

(Objectives) This study aimed to evaluate the surgical outcomes and functional parameters of lower urinary tract and bowel symptoms in patients who have undergone robot-assisted sacrocolpopexy (RASC) due to pelvic organ prolapse. (Patients and methods) This retrospective study included 110 consecutive RASC cases in the urology department of Ageo Central General Hospital, Japan, from November 2020 to October 2021. The medical records of these patients were retrieved. Data on uroflowmetry, post-void residual urine test, and self-administered questionnaires on urination and defecation were assessed. (Results) The mean operating time was 146 min, and the estimated blood loss was 14.8 ml. The intraoperative, postoperative, and severe complication rates of cases classified as Clavien-Dindo grade IIIa or higher were 0%, 9.1%, and 0%, respectively. The maximum flow rate and post-void residual volume of urine significantly improved after the operation. Similarly, the quality of life (QOL) scores and overactive bladder symptom score (OABSS), as well as the responses for the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) and Urinary Distress Inventory-6 (UDI-6), significantly improved one month after the operation and were sustained for six months. On the other hand, the total scores from the Constipation Scoring System (CSS) and the subscales of the Patient Assessment of Constipation (PAC) -QOL worsened. These scores, except for those of the PAC-QOL satisfaction subscale recovered to the preoperative levels; the PAC-QOL satisfaction subscale scores significantly improved six months postoperatively. The rates of de novo overactive bladder (OAB), stress urinary incontinence (SUI), and constipation one month postoperatively were 8%, 33%, and 10%, respectively. (Conclusions) RASC was performed safely in our institution with acceptable postoperative lower urinary tract and bowel outcomes.

Properties of gastroretentive sustained release tablets prepared by combination of melt/sublimation actions of L-menthol and penetration of molten polymers into tablets.

A novel floating sustained release tablet having a cavity in the center was developed by utilizing the physicochemical properties of L-menthol and the penetration of molten hydrophobic polymer into tablets. A dry-coated tablet containing famotidine as a model drug in outer layer was prepared with a L-menthol core by direct compression. The tablet was placed in an oven at 80°C to remove the L-menthol core from tablet. The resulting tablet was then immersed in the molten hydrophobic polymers at 90°C. The buoyancy and drug release properties of tablets were investigated using United States Pharmacopeia (USP) 32 Apparatus 2 (paddle 100 rpm) and 900 ml of 0.01 N HCl. The L-menthol core in tablets disappeared completely through pathways in the outer layer with no drug outflows when placed in an oven for 90 min, resulting in a formation of a hollow tablet. The hollow tablets floated on the dissolution media for a short time and the drug release was rapid due to the disintegration of tablet. When the hollow tablets were immersed in molten hydrophobic polymers for 1 min, the rapid drug release was drastically retarded due to a formation of wax matrices within the shell of tablets and the tablets floated on the media for at least 6 h. When Lubri wax® was used as a polymer, the tablets showed the slowest sustained release. On the other hand, faster sustained release properties were obtained by using glyceryl monostearate (GMS) due to its low hydrophobic nature. The results obtained in this study suggested that the drug release rate from floating tablets could be controlled by both the choice of hydrophobic polymer and the combined use of hydrophobic polymers.

[A case report of ureteropelvic junction obstruction and multiple renal stones associated with nutcracker syndrome].

A 20 year-old man presented to emergency room with severe left-sided flank pain. Urinalysis showed hematuria and he was referred to the urology department. KUB, DIP and retrograde pyelography (RP) revealed multiple renal stones, left hydronephrosis (grade 2) and ureteropelvic junction obstruction (UPJO). Abdominal CT revealed shortened nutcracker distance and renal angiography showed left renal vein hypertension. From these findings, diagnosis of nutcracker syndrome was made. Transposition of the left renal vein, dismembered pyeloplasty and left pyelolithotomy were performed simultaneously. 2 months after the procedure, his symptom and hematuria disappeared. 3 months after the procedure, DIP revealed improvement of hydronephrosis (grade 1) and CT showed elongation of nutcracker distance. In 12 months follow-up, there was no recurrence of symptom and hydonephrosis. To the best our knowledge, there has been no report of UPJO associated with nutcracker syndrome and the simultaneous treatment for the both diseases.

Symptomatic interdural cerebrospinal fluid collections after surgery for idiopathic spinal cord herniation: illustrative case.

BACKGROUND: Idiopathic spinal cord herniation (ISCH) is very rare. Some reports have described postoperative ventral cerebrospinal fluid (CSF) collections in patients with ISCH; however, such collections are asymptomatic in most patients, and there is no consensus regarding whether they are part of the natural history or a complication. OBSERVATIONS: A 30-year-old man with ISCH underwent direct closure of a duplicated dura mater. Eight months postoperatively, he developed reworsening of right lower limb paresis and new severe right arm pain and paresis. Three-dimensional magnetic resonance imaging revealed ventral CSF collections, which the authors judged as the responsible lesions. The authors initially considered these collections to be present in the epidural space, extradurally compressing the dural sac and resulting in myelopathy. An epidural blood patch failed; however, a CSF drainage test resulted in dramatic improvement. The authors therefore determined that the CSF collections were located in the interdural space, not the epidural space. A lumboperitoneal (LP) shunt was performed to reduce the CSF pressure. The patient's symptoms improved immediately postoperatively. He had developed no recurrence of symptoms 6 months after surgery. LESSONS: Ventral interdural CSF collections after ISCH surgery can cause reworsening of myelopathy and may be cured by a LP shunt to control CSF pressure.

Target Embolization of Dilated Post-PICA Segment for Ruptured PICA-Involved Type Vertebral Artery Dissecting Aneurysm.

Objective: In parent artery occlusion (PAO) for ruptured vertebral artery dissecting aneurysms (RVADA), target embolization using coils in a short segment to occlude only the vasodilated area containing the rupture point is selected as a first-choice procedure at our institute. We focused on RVADA involving the posterior inferior cerebellar artery (PICA) and evaluated the treatment results. Methods: This study consisted of eight cases with RVADA involving the PICA which were treated between October 2007 and January 2020. Based on radiological findings such as the bleb, the rupture points were located at the affected vertebral artery (VA) distal to PICA in all cases. Target embolization, by which only coiling at the dilated segment distal to the VA was performed. We aimed to preserve blood flow to the PICA. The incidence and extent of medullary infarctions, and neurological outcome were retrospectively assessed. Results: Regarding the diameter of bilateral VA, there were no differences in six cases while the affected VA with RVADA were larger in the remaining two cases. PICA was preserved in all cases but one in which occlusion of complementary PICA was observed. Postoperative medullary infarction was not noted. There was no rebleeding during the follow-up period. However, recanalization of the VA was observed in four cases and additional coil embolization was performed. All patients were discharged with a good outcome (modified Rankin Scale [mRS] 0; seven patients, mRS 2; one patient). Conclusion: Target embolization preserving the PICA in PICA-involved type RVADA was considered to be an effective treatment method for cases whose rupture point was located in the VA distal to PICA orifice.

Prediction of breast cancer sensitivity to neoadjuvant chemotherapy based on status of DNA damage repair proteins.

INTRODUCTION: Various agents used in breast cancer chemotherapy provoke DNA double-strand breaks (DSBs). DSB repair competence determines the sensitivity of cells to these agents whereby aberrations in the repair machinery leads to apoptosis. Proteins required for this pathway can be detected as nuclear foci at sites of DNA damage when the pathway is intact. Here we investigate whether focus formation of repair proteins can predict chemosensitivity of breast cancer. METHODS: Core needle biopsy specimens were obtained from sixty cases of primary breast cancer before and 18-24 hours after the first cycle of neoadjuvant epirubicin plus cyclophosphamide (EC) treatment. Nuclear focus formation of DNA damage repair proteins was immunohistochemically analyzed and compared with tumor response to chemotherapy. RESULTS: EC treatment induced nuclear foci of gammaH2AX, conjugated ubiquitin, and Rad51 in a substantial amount of cases. In contrast, BRCA1 foci were observed before treatment in the majority of the cases and only decreased after EC in thirteen cases. The presence of BRCA1-, gammaH2AX-, or Rad51-foci before treatment or the presence of Rad51-foci after treatment was inversely correlated with tumor response to chemotherapy. DNA damage response (DDR) competence was further evaluated by considering all four repair indicators together. A high DDR score significantly correlated with low tumor response to EC and EC + docetaxel whereas other clinicopathological factors analyzed did not. CONCLUSIONS: High performing DDR focus formation resulted in tumor resistance to DNA damage-inducing chemotherapy. Our results suggested an importance of evaluation of DDR competence to predict breast cancer chemosensitivity, and merits further studying into its usefulness in exclusion of non-responder patients.

Evaluation of CD56 and CD57 immunostainings for discrimination between endocrine ductal carcinoma in situ and intraductal papilloma.

Endocrine ductal carcinoma in situ (E-DCIS) is an intraductal carcinoma characterized by endocrine features and expression of neuroendocrine markers. E-DCIS and intraductal papilloma (IDP) resemble in their clinical features. However, the former is an intraductal carcinoma, and the latter is an intraductal benign lesion. It is sometimes difficult to distinguish E-DCIS from IDP because both can show near solid intraductal cellular proliferation. Discrimination between lesions is important not only histopathologically, but also clinically. This study aimed to evaluate the applicability of CD56 and CD57 for the discrimination between E-DCIS and IDP. Specimens were obtained from 17 E-DCIS patients as the subject group, and 27 IDP patients as the control group, diagnosed in St Marianna University Hospital. E-DCIS was diagnosed using Chromogranin A, Synaptophysin, and Grimelius stainings by the premise of histopathological features. These specimens were subjected to CD56, CD57 immunostainings. Staining results were compared between E-DCIS and IDP. In our study, CD56 revealed significant differences for distinguishing E-DCIS from IDP as determined by Fisher's test (cutoff: not less than 33-67%< immunopositivity, P < 0.05). We found that not only E-DCIS but also IDP revealed immunopositivity for CD56. However, it is considered that E-DCIS diagnosis is possible by diffuse immunopositivity of CD56 after having been based on histopathology.

Results of Therapy Using Oral Anticoagulants in the Acute Phase after Mechanical Thrombectomy.

Objective: The usage of oral anticoagulants (OACs) in the acute phase of cerebral infarction has increased, but the optimal timing for starting OACs after mechanical thrombectomy (MT) is unclear. We report the usage of OACs after MT at our hospital and evaluated the outcomes. Methods: OACs were selected as secondary preventive drugs for 64 patients who underwent MT for anterior circulatory embolism between July 2016 and January 2019. Of the 64 patients, 28 and 36 received direct oral anticoagulants (DOACs) and warfarin (Wf), respectively. We compared the frequency of intracranial hemorrhage in the acute phase and that of recurrent cerebral infarction within 30 days. Results: The median diffusion-weighted imaging-Alberta Stroke Program Early Computed Tomography Scores + white matter (DWI-ASPECTS + W) score at admission was 7.5 (IQR 6-9)/8 (IQR, 6-9) in the DOACs group/Wf group. The rate of recanalization with modified thrombolysis in cerebral infarction (TICI) ≥2B by MT was 89.3/80.6%. In patients with subarachnoid hemorrhage (SAH) associated with MT and patients with hemorrhagic transformation (HT) on MRI the next day, administration was started after hemostasis. The median timing of the first anticoagulant administration was 3 (IQR, 2-4)/2 (IQR, 1-4) days. In the case of no HT the next day, the rate of new HT after 1 week was 7.1%/29.1%. In the case of HT the next day, the rate of HT deterioration the next day was 7.1%/16.6%. The percentage of symptomatic bleeding was 0%/2.8%. The percentage of recurrent cerebral infarction within 30 days was 0%/2.8%. Conclusion: OACs in the acute phase after MT can be safely used and are expected to be effective at preventing recurrence.

BRCA1 ubiquitinates RPB8 in response to DNA damage.

The breast and ovarian tumor suppressor BRCA1 catalyzes untraditional polyubiquitin chains that could be a signal for processes other than proteolysis. However, despite intense investigations, the mechanisms regulated by the enzyme activity remain only partially understood. Here, we report that BRCA1-BARD1 mediates polyubiquitination of RPB8, a common subunit of RNA polymerases, in response to DNA damage. A proteomics screen identified RPB8 as a protein modified after epirubicin treatment in BRCA1-dependent manner. RPB8 interacted with BRCA1-BARD1 and was polyubiquitinated by BRCA1-BARD1 in vivo and in vitro. BRCA1-BARD1 did not destabilize RPB8 in vivo but rather caused an increase in the amount of soluble RPB8. Importantly, RPB8 was polyubiquitinated immediately after UV irradiation in a manner sensitive to BRCA1 knockdown by RNA interference. Substitution of five lysine residues of RPB8 with arginine residues abolished its ability to be ubiquitinated while preserving its polymerase activity. HeLa cell lines stably expressing this ubiquitin-resistant form of RPB8 exhibited UV hypersensitivity accompanied by up-regulated caspase activity. Our findings suggest that ubiquitination of a common subunit of RNA polymerases is a mechanism underlying BRCA1-dependent cell survival after DNA damage.

Involvement of kinesin family member 2C/mitotic centromere-associated kinesin overexpression in mammary carcinogenesis.

To elucidate the molecular mechanisms of mammary carcinogenesis and discover novel therapeutic targets for breast cancer, we previously carried out genome-wide expression profile analysis of 81 breast cancer cases by means of cDNA microarray coupled with laser microbeam microdissection of cancer cells. Among the dozens of transactivated genes, in the present study we focused on the functional significance of kinesin family member 2C (KIF2C)/mitotic centromere-associated kinesin (MCAK) in the growth of breast cancer cells. Northern blot and immunohistochemical analyses confirmed KIF2C/MCAK overexpression in breast cancer cells, and showed that it is expressed at undetectable levels in normal human tissues except the testis, suggesting KIF2C/MCAK to be a cancer-testis antigen. Western blot analysis using breast cancer cell lines revealed a significant increase in the endogenous KIF2C/MCAK protein level and its phosphorylation in G(2)/M phase. Treatment of breast cancer cells with small interfering RNA against KIF2C/MCAK effectively suppressed KIF2C/MCAK expression and inhibited the growth of the breast cancer cell lines T47D and HBC5. In addition, we found that KIF2C/MCAK expression was significantly suppressed by ectopic introduction of p53. These findings suggest that overexpression of KIF2C/MCAK might be involved in breast carcinogenesis and is a promising therapeutic target for breast cancers.