CDK12 and HER2 coamplification in two urothelial carcinomas with rapid and aggressive clinical progression

Cyclin‐dependent kinase 12 (CDK12), one of the key factors associated with DNA damage response pathways, is located on chromosome 17 proximal to Erb‐B2 receptor tyrosine kinase 2 (ERBB2). In this report, CDK12 and ERBB2 coamplification was detected by targeted next‐generation sequencing in two urothelial carcinomas. The staining intensity of the CDK12 and human epidermal growth factor receptor‐2 proteins was associated with the prognosis of each urothelial carcinoma case. Our results suggest that CDK12 coamplification with ERBB2 might be associated with tumor aggressiveness and contribution to cancer pathogenesis. Therapies targeting CDK12 should be developed for these patients.     

AUGMENTATION OF ANGIOTENSIN II RELEASE FROM ISOLATED MESENTERIC ARTERIES OF WISTAR-KYOTO AND SPONTANEOUSLY HYPERTENSIVE RATS FOLLOWING NEPHRECTOMY

1. We previously reported that angiotensin II release from the mesenteric arteries of Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) increased in a time-dependent manner as a result of the isolation of the arteries and perfusion. This phenomenon appeared to be due to the withdrawal of circulating angiotensin II (AII). 2. The purpose of the present study was to test the hypothesis that vascular AII generation may be negatively regulated by circulating AII in WKY and SHR, and to clarify the role of this vascular angiotensin II in the sustained hypertension of SHR following nephrectomy. 3. The mesenteric arteries from kidney-intact and nephrectomized WKY and SHR were perfused and the amount of AII released into the perfusate was measured. The effects of the angiotensin converting enzyme inhibitor, captopril, and the effects of supplementation of renal renin and circulating angiotensins to nephrectomized rats, by blood exchange between kidney-intact and nephrectomized rats, on AII release were examined to clarify the pathway of vascular AII generation after nephrectomy. 4. Nephrectomy caused augmentation of vascular AII release both in WKY and SHR in spite of the abolishment of circulating renin. Captopril reduced this enhanced release of AII, but blood exchange did not affect it. There was no significant difference in these responses between WKY and SHR. 5. These results suggest that WKY and SHR have in common a potent pathway for production of vascular AII in response to the withdrawal of circulating AII, although this pathway is not responsible for the sustained hypertension of SHR after nephrectomy. The precise pathophysiological role of this pathway remains to be elucidated.     

Drosera rotundifolia and Drosera tokaiensis suppress the activation of HMC-1 human mast cells

Ethnopharmacological relevance

Several Northern Hemisphere Drosera species have been used in the therapy of respiratory tract infections as the traditional medicine Droserae Herba.

Aim of the study

To determine the anti-inflammatory effects of Drosera species and to investigate a substitute material for Droserae Herba, we examined the effect of extracts of Drosera rotundifolia, Drosera tokaiensis and Drosera spatulata on activated T cell membrane (aTc-m)-induced inflammatory gene expression in HMC-1 human mast cells.

Materials and methods

Drosera rotundifolia, Drosera spatulata and Drosera tokaiensis were collected in Japan. Herbs were extracted with 80% EtOH, and subsequently applied to OASIS HLB column. HMC-1 cells were treated with each Drosera column-adsorbed fraction for 15 min, and subsequently added to aTc-m and incubated for 16 h. Inflammatory gene and protein expressions were determined by DNA microarray, RT-PCR and Western blotting.

Results

Drosera rotundifolia and Drosera tokaiensis fractions, but not the Drosera spatulata fraction, suppressed inflammatory gene expression induced by aTc-m in HMC-1 cells.

Conclusions

Drosera rotundifolia and Drosera tokaiensis suppressed activation of HMC-1 cells induced by aTc-m. Since the Drosera tokaiensis fraction was more effective than the traditionally used Drosera rotundifolia, Drosera tokaiensis is a likely substitute as a source of Droserae Herba.     

Retroperitoneal primary mucinous adenocarcinoma with a mural nodule of anaplastic tumor: a case report and literature review.

A 38-year-old female presented with a lower abdominal mass. During the operation the mass was found to be retroperitoneal and was excised. Gross examination revealed a mucin-containing cystic lesion with a mural nodule. On microscopic examination, the cystic areas were lined by an invasive mucinous adenocarcinoma and the nodule was composed of an anaplastic sarcomatoid tumor that was immunoreactive for cytokeratin. This present case is the 21st example of a retroperitoneal primary mucinous cystadenocarcinoma and the fourth with a mural nodule. Three of four cases with a mural nodule, including our case, had a rapidly fatal outcome.     

Clinical features of patients with obsessive-compulsive disorder showing different pharmacological responses]

BACKGROUND: Although selective serotonin reuptake inhibitors (SSRIs) are the mainstay of pharmacological treatment for obsessive-compulsive disorder (OCD), some OCD patients do not show improvement. Sometimes, the addition of a low-dose atypical antipsychotic, such as risperidone, or olanzapine, to ongoing SSRI treatment has been shown to be effective. However, there are patients who still show no response after trials with this augmentation therapy. In the present study, we examined the clinical features of OCD patients who showed different responses to pharmacological treatment. SUBJECTS AND METHOD: Fifty OCD patients were divided into three groups according to their pharmacological responses: responders to SSRI (group A: n= 25), responders to SSRI with an atypical antipsychotic (group B: n= 15), and non-responders to both SSRI and SSRI with an atypical antipsychotic (group C: n= 10). We examined the clinical features such as age, sex, age of onset, duration of illness, types of obsessive-compulsive symptoms, severity, improvement after treatment, insight into disease, depression, comorbidity, involving family members in compulsive or ritualistic behavior, and the level of social adaptation of each OCD group. RESULTS: Twenty five patients showed a good response to SSRI monotherapy, 15 showed a response to antipsychotic augmentation, and 10 were non-responders to both SSRI and SSRI with an atypical antipsychotic. Significantly lower insight levels were observed only in group B and higher depressive levels in group C. OCD patients who were refractory to SSRI monotherapy showed comorbidity at a significantly higher frequency. OCD patients in group A showed significantly greater improvement, and group B showed inferior social adaptation after treatment. There were no significant differences in age, sex, age of onset, duration of illness, severity, involving family members in compulsive or ritualistic behavior, and social adaptation before treatment in the three OCD groups. CONCLUSION: There were differences in the clinical features of OCD patients who showed different responses to pharmacological treatment. Our results suggest that OCD is clinically and biologically heterogeneous. It may be important to divide OCD patients into subgroups for future studies.     

Hyperaemia prior to acute cerebral swelling in severe head injuries: The role of transcranial doppler monitoring

Summary Acute cerebrovascular congestion after a closed head injury is significantly related to intracranial hypertension. As an indirect method of cerebral blood flow measurement, transcranial doppler sonography (TCD) provides a rapid and noninvasive assessment of cerebral haemodynamics, including hyperaemic conditions.TCD examinations was serially performed in 35 patients with severe head injury with intact cerebral circulation; i.e. the mean flow velocity (MFV) patterns of the middle cerebral artery (MCA) did not show signs of cerebral circulatory arrest such as systolic spike, to and fro, or no flow. The results showed that the MFV of the MCAs and ipsilateral extracranial internal carotid arteries (ICAs) in 9 of these patients increased sharply and pulsatility index (PI) decreased during 48–96 hours after the injury. This was soon followed by patterns of high intracranial resistance, consistent with elevated intracranial pressure (ICP) in monitored patients and acute brain swelling on repeated computed tomographic (CT) scans. The correlation between increased MFVs, decreased PIs, and cerebral haemodynamic changes leading to acute brain swelling is discussed.The number of patients who ended with severe disability, vegetative state, or death was 66% in this group of 9 patients, compared to only 34% for the 35 patients overall with severe head injury. Though the morbidity and mortality rates largely depend on the primary injury, the presence of acute cerebral swelling aggravate the grave course in these patients. And the ability of TCD to monitor the hyperaemic state prior to oedema should lead us to adjust the therapy in order to minimize the secondary insult related to intracranial hypertension.