Pulmonary Tumor Thrombotic Microangiopathy With Versican Expression in a Patient With Advanced Gastric Cancer: A Case Report of a Rare Autopsy.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare but fatal complication of a malignant tumor that causes rapidly progressive pulmonary hypertension (PH). We report the case of a 70-year-old Japanese man who died of respiratory failure during chemotherapy for gastric cancer and was diagnosed with PTTM at autopsy. The autopsy revealed PTTM-specific histological findings, such as tumor emboli with fibrin-rich clots and fibrocellular intimal proliferation in the vessels. The cancer cells were immunohistochemically positive for vascular endothelial growth factor and platelet-derived growth factor, whereas the thickened intima of the pulmonary arteries was positive for versican (VCAN). As VCAN is an extracellular matrix proteoglycan that is dramatically increased in vascular lesions of pulmonary arterial hypertension, this case demonstrates that VCAN is also involved in the pathophysiology of PTTM.

Glioblastoma with concomitant moyamoya vasculopathy in neurofibromatosis type 1: illustrative case.

BACKGROUND: In a case of concurrent glioblastoma and moyamoya vasculopathy, it is arduous to safely perform surgery because the brain is highly vulnerable and collaterals are sometimes well developed. In addition, radiotherapy carries a risk of aggravating moyamoya vasculopathy, and chemotherapeutic agents also have a risk of interfering with collateral development. OBSERVATIONS: A 48-year-old woman with neurofibromatosis type 1 was admitted because of left hemiparesis and hemispatial neglect. Brain imaging studies revealed a large mass with peripheral enhancement in the right frontal lobe and occlusion of the bilateral middle cerebral arteries with an abnormal vascular network at the base of the brain. Total tumor resection was performed, and the pathological diagnosis was isocitrate dehydrogenase-mutant glioblastoma. Radiotherapy with a total dose of 60 Gy was delivered with concurrent temozolomide, and thereafter six cycles of adjuvant temozolomide were given. Progression of moyamoya vasculopathy without symptoms was observed after the completion of each of radiotherapy and adjuvant temozolomide. LESSONS: The authors present the first adult case of glioblastoma with moyamoya vasculopathy. Careful consideration and attention should be given throughout treatment to avoiding moyamoya vasculopathy-related ischemic and hemorrhagic events. Although the patient did not exhibit neurological deterioration, progression of moyamoya vasculopathy occurred early after radiotherapy and continued thereafter.

[Concomitant Cardiac and Pulmonary Operation on an Elderly Patient:Report of a Case].

An 83-year-old woman was admitted because of dyspnea. Transthoracic echocardiography revealed severe aortic valve stenosis with a systolic gradient of 105 mmHg. Coronary angiography showed 75% stenosis at segment 1. Computed tomography( CT) of the chest revealed a mass, of 15 mm in diameter, in the right segment 1 of the lung. She was diagnosed with severe aortic valve stenosis, right coronary artery stenosis, and a lung tumor suspected to be lung cancer. We performed right lobe partial resection, aortic valve replacement and coronary artery bypass grafting through a median sternotomy. The tumor was diagnosed as adenocarcinoma by pathological examination. The postoperative course was uneventful, and she was discharged three weeks after the operation.

A case presenting as fatal subarachnoid hemorrhage due to segmental arterial mediolysis associated with Crohn's disease.

BACKGROUND: Segmental arterial mediolysis (SAM) is a rare arterial pathology and can cause rupture or dissection of the intracranial arterial wall. The etiology is unveiled, but vasospastic stimuli such as migraine are considered as a possible cause of SAM. We present the first case of subarachnoid hemorrhage (SAH) due to SAM associated with Crohn's disease and migraine, and discuss the possible contribution of Crohn's disease to the development of SAM besides migraine. CASE DESCRIPTION: A 33-year-old man with Crohn's disease, which had been treated with adalimumab, repeatedly underwent 3-tesla magnetic resonance (MR) imaging and angiography for severe headache due to migraine and the subsequent development of fatigue in the left arm and both legs. At 7 months after the last MR imaging studies showing no abnormalities, he had a sudden onset of severe SAH, which was caused by rupture or dissection of the terminal portion in the right internal carotid artery. As his brain-stem reflexes were absent, the patient was conservatively treated and died 6 days after the ictus. By postmortem histopathological examination, SAM was diagnosed as the cause of SAH. Vasa vasorum was also observed around the rupture point. CONCLUSIONS: Our case suggests that: 1) the formation of vasa vasorum may be an antecedent pathology for vessel rupture of the fragile arterial wall affected by SAM, and 2) vasospastic nature of both Crohn's disease and migraine may contribute to the development of intracranial SAM.

Heterogeneous induction of an invasive phenotype in prostate cancer cells by coculturing with patient-derived fibroblasts.

Prostate cancer (PCa) cells frequently invade the surrounding stroma, leading to heterogeneous formation of structural atypia. The surrounding stroma contains multiple functionally diverse populations of fibroblasts that trigger numerous changes in PCa cells including motility. Thus, we hypothesized that direct or indirect contact of PCa cells with fibroblasts determines an invasive phenotype in PCa cells. We investigated the effects of 10 different patient-derived fibroblast lines on the three-dimensional (3D) morphogenesis of PCa cells growing on a viscous substrate in vitro. When grown alone, all 10 patient-derived fibroblast lines clumped on the viscous substrate, whereas the human androgen-sensitive PCa cell line LNCaP did not. Cocultures of LNCaP cells with seven of the patient-derived fibroblast lines (PrSC, pcPrF-M5, pcPrF-M7, pcPrF-M23, pcPrF-M24, pcPrF-M28, and pcPrF-M31) formed a thick fibroblast layer that resembled human prostate stromal structures. In contrast, cocultures of LNCaP cells with the remaining three fibroblast lines (NPF-M13, pcPrF-M10, and pcPrF-M26) did not form a thick fibroblast layer. Of the seven fibroblast lines that caused thick layer formation, four patient-derived fibroblast lines (PrSC, pcPrF-M5, pcPrF-M28, and pcPrF-M31) induced an invasive phenotype in LNCaP cells with a cord-like infiltrating growth pattern, whereas the other three fibroblast lines (pcPrF-M7, pcPrF-M23, and pcPrF-M24) induced no or a very weak invasive phenotype. Using cell culture inserts, none of the four patient-derived fibroblast lines that induced an invasive phenotype (PrSC, pcPrF-M5, pcPrF-M28, and pcPrF-M31) affected CDH1 mRNA expression in LNCaP cells; yet, two patient-derived fibroblast lines (pcPrF-M5 and pcPrF-M28) increased CDH2 mRNA expression in LNCaP cells, whereas the other two fibroblast lines (PrSC and pcPrF-M31) did not. These results suggest that the existence of multiple functionally diverse populations of fibroblasts in PCa tissue may be responsible for the diversity in PCa cell invasion, leading to heterogeneous formation of structural atypia.

A Ruptured Blood Blister-Like Aneurysm Associated with Intraperitoneal Hemorrhage due to Segmental Arterial Mediolysis: A Case Report and Literature Review.

BACKGROUND: Segmental arterial mediolysis (SAM) is a rare non-atherosclerotic, noninflammatory vascular disease, characterized by mediolysis. We report an extremely rare case of subarachnoid hemorrhage (SAH) due to a ruptured blood blister-like aneurysm (BBA) of the internal carotid artery associated with SAM-related arteriopathy. CASE DESCRIPTION: We experienced a case of SAH followed by intraperitoneal hemorrhage that occurred 12 days after the SAH onset. SAH was caused by a ruptured BBA of the internal carotid artery, which was treated by trapping with high-flow bypass. Intraperitoneal hemorrhage was caused by a rupture of a posterior inferior pancreaticoduodenal artery (PIPDA) aneurysm, which induced hypovolemic shock resulting in death in spite of endovascular internal trapping. Postmortem pathologic examination revealed that the PIPDA pseudoaneurysm was due to SAM. CONCLUSIONS: We should pay attention to the association of SAM, which is a potentially life-threatening pathology when treating cerebral BBAs.

[Rapidly Growthing Mediastinal Cystic Teratoma with Suggestive Perforation by Infection in Pregnancy].

The patient was a 34-year-old female and was 32 weeks pregnant. She was admitted to our department because of mediastinal cyst with infection. She complained of chest pain. Chest computed tomography(CT) revealed the rapid growth of anterior mediastinal tumor. The pain increased after 2 days and magnetic resonance imaging (MRI) suggested the rupture of teratoma. After delivery by Caesarean section, we performed abscess drainage, to stabilize the patient's condition and thereafter the resection of mediastinal teratoma with partial resection of right lung was performed. Histological findings showed a mature teratoma.

Arylpyrrolyldiketone Boron Complexes Exhibiting Various Anion-Binding Modes Based on Dynamic Conformation Changes.

Arylpyrrolyldiketone boron complexes as anion-responsive π-electronic molecules were synthesized by Claisen condensations of acetylpyrrole and corresponding aryl esters. The synthesized π-electronic molecules exhibited anion-binding behavior with various binding modes including pyrrole-inverted and non-inverted [1+1]-type anion complexes as well as [2+1]-type complexes owing to the presence of only a single pyrrole ring. Furthermore, solid-state ion-pairing assemblies, comprising receptor-anion complexes and countercations, were constructed based on fairly planar [2+1]-type complexes.

Multiple animal positioning system shows that socially-reared mice influence the social proximity of isolation-reared cagemates.

Social relationships are a key determinant of social behaviour, and disruption of social behaviour is a major symptom of several psychiatric disorders. However, few studies have analysed social relationships among multiple individuals in a group or how social relationships within a group influence the behaviour of members with impaired socialisation. Here, we developed a video-analysis-based system, the Multiple-Animal Positioning System (MAPS), to automatically and separately analyse the social behaviour of multiple individuals in group housing. Using MAPS, we show that social isolation of male mice during adolescence leads to impaired social proximity in adulthood. The phenotype of these socially isolated mice was partially rescued by cohabitation with group-housed (socially-reared) mice, indicating that both individual behavioural traits and those of cagemates influence social proximity. Furthermore, we demonstrate that low reactive behaviour of other cagemates also influence individual social proximity in male mice.

Sexual odor preference and dopamine release in the nucleus accumbens by estrous olfactory cues in sexually naïve and experienced male rats.

Sexual behavior is a natural reward that activates mesolimbic dopaminergic system. Microdialysis studies have shown that extracellular level of dopamine (DA) in the nucleus accumbens (NAcc) significantly increases during copulation in male rats. The NAcc DA level is also known to be increased during the presentation of a sexually receptive female before mating. This rise in DA was probably associated with sexual motivation elicited by incentive stimuli from the receptive female. These microdialysis studies, however, did not thoroughly investigated if olfactory stimuli from estrous females could significantly increase the extracellular DA in the NAcc of male rats. The present study was designed to examine systematically the relationship between the expression of preference for the olfactory stimuli from estrous females and the effects of these stimuli on the extracellular DA levels in the NAcc measured by in vivo microdialysis in male Long-Evans (LE) rats. We used two types of olfactory stimuli, either airborne odors (volatile stimuli) or soiled bedding (volatile plus nonvolatile stimuli). The sexually experienced male rats, which experienced six ejaculations, significantly preferred both of these olfactory stimuli from estrous females as opposed to males. Exposure to these female olfactory stimuli gradually increased extracellular DA in the NAcc, which reached significantly higher level above baseline during the period following the removal of the stimuli although not during the 15-min stimulus presentation period. The sexually naïve male rats, on the other hand, showed neither preference for olfactory stimuli from estrous females nor increase in the NAcc DA after exposure to these stimuli. These data suggest that in male LE rats olfactory stimuli from estrous females in and of themselves can be conditional cues that induce both incentive motivation and a significant increase in the NAcc DA probably as a result of being associated with sexual reward through copulatory experience.

Regulation of sexual odor preference by sex steroids in the posterodorsal medial amygdala in female rats.

Our previous study in male rats demonstrated that bilateral administration of flutamide, an androgen receptor (AR) antagonist, into the posterodorsal medial amygdala (MePD) increased the time sniffing male odors to as high as that sniffing estrous odors, eliminating the preference for estrous odors over male odors. This made us speculate that under blockade of AR in the MePD, testosterone-derived estrogen acting on the same brain region arouses interest in male odors which is otherwise suppressed by concomitant action of androgen. In cyclic female rats, endogenous androgen has been thought to be involved in inhibitory regulation of estrogen-activated sexual behavior. Thus, in the present study, we investigated the possibility that in female rats the arousal of interest in male odors is also normally regulated by both estrogen and androgen acting on the MePD, as predicted by our previous study in male rats. Implantation of either the estrogen receptor blocker tamoxifen (TX) or a non-aromatizable androgen 5α-dihydrotestosterone (DHT) into the MePD of ovariectomized, estrogen-primed female rats eliminated preference for male odors over estrous odors by significantly decreasing the time sniffing male odors to as low as that sniffing estrous odors. The subsequent odor discrimination tests confirmed that the DHT and TX administration did not impair the ability to discriminate between male and estrous odors. These results suggest that in estrous female rats estrogen action in the MePD plays critical roles in the expression of the preference for male odors while androgen action in the same brain region interferes with the estrogen action.

ASF-4-1 fibroblast-rich culture increases chemoresistance and mTOR expression of pancreatic cancer BxPC-3 cells at the invasive front in vitro, and promotes tumor growth and invasion in vivo.

Pancreatic cancer develops dense stromal tissue through the desmoplastic reaction. The aim of the present study was to assess the effects of a fibroblast-rich environment on the malignant potential of pancreatic cancer. Cells from the human pancreatic cancer cell line BxPC-3 were mixed at a ratio of 1:3 (fibroblast-rich) or 1:1 (fibroblast-poor) with cells from the human skin fibroblast line ASF-4-1. In the fibroblast-rich co-culture, tumor budding was observed and BxPC-3 cells were found to be more resistant to gemcitabine than those in the fibroblast-poor co-culture. Immunohistochemistry revealed that the expression of mammalian target of rapamycin was increased at the invasive front of fibroblast-rich co-cultures. In addition, in mouse xenografts of fibroblast-rich co-cultures, tumors were larger and had a higher Ki-67 index compared with that of the fibroblast-poor co-culture xenografts. These results indicate that fibroblast-rich co-cultures may promote the malignant potential of the pancreatic cancer cell line BxPC-3, both in vitro and in vivo.

Inflammatory suppressive effect of prostate cancer cells with prolonged exposure to transforming growth factor ß on macrophage-differentiated cells via downregulation of prostaglandin E2.

Transforming growth factor ß1 (TGFß1) regulates a variety of cellular functions, including cell growth, apoptosis and differentiation. The aim of the current study was to investigate the alterations of phenotypic events in the long-term exposure of prostate cancer (PCa) cells to TGFß1 and its effect on macrophage-differentiated cells. The PCa cell line, PC-3, and the subclone, M1, were exposed to TGFß1 for short- or long-term periods. TGFß1 signaling was assessed by Smad3 phosphorylation, and non-canonical signaling was analyzed by quantitative polymerase chain reaction-based regulatory gene expression profiles. TGFß1-exposed PCa cells were also co-cultured with phorbol 12-myristate 13-acetate (PMA)-treated THP-1 macrophages as a model of the tumor microenvironment. The phosphorylation of Smad3 in the PCa cells with long-term exposure was lower than that in the PCa cells with short-term exposure. Interleukin-6 mRNA expression in the PMA-treated THP-1 macrophages was significantly downregulated by co-culture with the PCa cells with long-term exposure. Cyclooxygenase-2 expression in the long-term TGFß1-exposed PCa cells was lower than that in the control PCa cells, and the production of prostaglandin E2 (PGE2) in the long-term TGFß1-exposed PCa cells was also significantly lower. The results of the current study demonstrated that the long-term TGFß1 exposure of PCa cells induces phenotypic changes, including the downregulation of PGE2 production. This indicates that prolonged TGFß-exposed PCa cells may change the cytokine production of macrophages in the tumor microenvironment.

[A CR case of colorectal cancer given 39 courses of FOLFOX].

We report a CR case of advanced rectal cancer successfully treated with 39 courses of mFOLFOX6. The patient was a 29-year-old female with Stage IV rectal cancer. At first she was given IFL together with radiotherapy. It took effect for three months, and the therapeutic effect was PR, but interstitial pneumonia developed. Therefore, we shifted to mFOLFOX6, and she was treated with 39 courses. Grade 1 appeared several times for peripheral neuropathy, but recovered immediately. If we could control peripheral neuropathy with FOLFOX, it was thought that long-term survival could / be expected.