[Pathological classification of malignant peritoneal mesothelioma and comparative analysis with peritoneal carcinomatosis].

Objective: To analyze the pathological classification of malignant peritoneal mesothelioma (MPeM) and screen the immunohistochemical markers that can distinguish MPeM from peritoneal metastatic carcinoma (PC) . Methods: In June 2020, the pathological results of peritoneal biopsy of 158 MPeM and 138 PC patients from Cangzhou Central Hospital, Cangzhou People's Hospital, and Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine from May 2011 to July 2019 were retrospectively analyzed, and the pathological classifications of MPeM in Cangzhou were summarized. Immunohistochemical markers of MPeM and PC patients were analyzed, and receiver operating characteristic curve (ROC curve) was drawn for differential diagnosis of MPeM and PC. Results: There were 55 male and 103 female MPeM patients in Cangzhou, with an average age of 57.1 years old. The asbestos exposure rate was 91.14% (144/158). The most common pathological classifications were cutaneous type, accounting for 90.51% (143/158). There were significant differences in the expression of calreticulum protein, CK5/6, vimentin, D2-40, carcinoembryonic antigen (CEA) and tail type homologous nuclear gene transcription factor 2 (CDX-2) between MPeM and PC (P<0.05). Among the 6 positive markers, the sensitivity of calreticulum protein was the highest (0.905) and CEA was the lowest (0.428) . Conclusion: Calreticulum protein, CK5/6, vimentin, D2-40, CEA and CDX-2 may be used as specific markers to distinguish the diagnosis of MPeM from PC.

[Prognostic value of new TNM staging and serum CA125 in malignant peritoneal mesothelioma].

Objective: To explore the relationship between the new Tumor-Node-Metastasis (TNM) staging system and the serum CA125 level with the prognosis of malignant peritoneal mesothelioma (MPeM) . Methods: The clinical data of 74 patients with MPeM diagnosed by pathology and immunohistochemistry were collected from January 2005 to June 2016 in Cangzhou Central Hospital. According to the results of CT-peritoneal carcinoma index (PCI) , the tumor load was divided into T1 (PCI 1-10) , T2 (PCI 11-20) , T3 (PCI 21-30) and T4 (PCI 31-39) , combined with lymph node metastasis and extraperitoneal metastasis, a new TNM staging system was established. And serum CA125 level was measured in the same time. The median survival time of patients with MPeM, the effect of the new TNM staging system, and serum CA125 levels on their prognosis were retrospectively analyzed. Results: Among the 74 patients with MPeM, 25 (33.8%) cases were males and 49 (66.2%) cases were females. There were 8 cases with systemic chemotherapy, 8 cases with heated intraperitoneal chemotherapy, and 1 case with combination chemotherapy. 10 cases were T1, 22 cases were T2, 27 cases were T3, 15 cases were T4, 12 cases had lymph node metastasis and 10 cases had distant metastasis. The median survival time of T1, T2, T3 and T4 were 12, 10, 6 and 3 months respectively. There were 38 (77.6%) cases with high serum CA125 in all 49 cases who have been tested for CA125. The median survival time of positive group and negative group were 6 months and 11 months respectively. 68 (91.9%) patients had died by the end of collecting data. The median survival time was 8 months. Univariate analysis showed that there were significant differences in survival time between patients with different CT-PCI stages, serum CA125 levels, and with or without lymph node and extraperitoneal metastasis (P<0.05) . Multivariate analysis showed that CT-PCI was independent risk factors for the prognosis of MPeM (HR=2.203, 95%CI: 1.475-3.289) . Conclusion: The new TNM staging system and serum CA125 are important for the prognosis of patients with MPeM. Early detection, early diagnosis and comprehensive treatment can improve the survival time of patients with MPeM.

miR-194 inhibits gastric cancer cell proliferation and tumorigenesis by targeting KDM5B.

OBJECTIVE: MicroRNAs play critical roles in regulating gene expression and various cellular processes in human cancer malignant progression. The aim of the present study was to examine the expression pattern of miR-194 in gastric cancer (GC) and its biological role in tumor progression. MATERIALS AND METHODS: Using quantitative RT-PCR, we detected miR-194 expression in GC cell lines and primary tumor tissues. The proliferation, migration, and invasion assays were performed to investigate the effect of miR-194 on the GC cells. The target of miR-194 was predicted by TargetScan and confirmed by luciferase reporter assay. KDM5B expression was detected by Western blot. RESULTS: miR-194 was significantly down-regulated in GC tissues and cell lines. Over-expression of miRNA-194 could inhibit GC cell proliferation, migration, and invasion in vitro. Also, miR-194 inhibited tumor growth and progression in vivo. Dual luciferase-based reporter assay indicated direct regulation of KDM5B by miR-194. CONCLUSIONS: Our findings suggested that miR-194 directly targeted KDM5B and thereby acted as a tumor promoter in GC progression.

High expression of long noncoding RNA Sox2ot is associated with the aggressive progression and poor outcome of gastric cancer.

OBJECTIVE: The aim of our study was to investigate the expression of long non-coding RNA Sox2ot (Sox2ot) in gastric cancer (GC) patients and its association with clinicopathologic parameters and the prognosis. PATIENTS AND METHODS: Quantitative real-time polymerase chain reaction was performed to detect Sox2ot expression in 155 GC tissues and paired adjacent normal tissues. The relationships between Sox2ot expression and the clinicopathological features of GC patients were analyzed. Furthermore, overall survival (OS) and disease-free survival (DFS) were evaluated using the Kaplan-Meier method, and multivariate analysis was performed using the Cox proportional hazard analysis. RESULTS: Sox2ot expression levels were decreased in cancerous tissues compared to their corresponding non-cancerous controls (p < 0.01). Sox2ot expression was associated with T stage, distant metastasis and differentiation (p = 0.009, 0.034 and 0.001, respectively). In addition, patients with high Sox2ot expression tended to have poorer OS and DFS (p < 0.001, respectively). Finally, multivariate analysis showed Sox2ot expression was an independent prognostic factor for GC patients. CONCLUSIONS: Our findings showed that overexpressed Sox2ot was correlated with aggressive tumor behavior. Sox2ot may serve as a novel prognostic factor and a potential target to improve the long-term outcome of GC.

Changes in cardiac function after pedicle subtraction osteotomy in patients with a kyphosis due to ankylosing spondylitis.

Cardiac disease in patients with ankylosing spondylitis (AS) has previously been studied but not in patients with a kyphosis or in those who have undergone an operation to correct it. The aim of this study was to measure the post-operative changes in cardiac function of patients with an AS kyphosis after pedicle subtraction osteotomy (PSO). The original cohort consisted of 39 patients (33 men, six women). Of these, four patients (two men, two women) were lost to follow-up leaving 35 patients (31 men, four women) to study. The mean age of the remaining patients was 37.4 years (22.3 to 47.8) and their mean duration of AS was 17.0 years (4.6 to 26.4). Echocardiographic measurements, resting heart rate (RHR), physical function score (PFS), and full-length standing spinal radiographs were obtained before surgery and at the two-year follow-up. The mean pre-operative RHR was 80.2 bpm (60.6 to 112.3) which dropped to a mean of 73.7 bpm (60.7 to 90.6) at the two-year follow-up (p = 0.0000). Of 15 patients with normal ventricular function pre-operatively, two developed mild left ventricular diastolic dysfunction (LVDD) at the two-year follow-up. Of 20 patients with mild LVDD pre-operatively only five had this post-operatively. Overall, 15 patients had normal LV diastolic function before their operation and 28 patients had normal LV function at the two-year follow-up. The clinical improvement was 15 out of 20 (75.0%): cardiac function in patients with AS whose kyphosis was treated by PSO was significantly improved.

Decision making regarding spinal osteotomy and total hip replacement for ankylosing spondylitis: experience with 28 patients.

Few studies have examined the order in which a spinal osteotomy and total hip replacement (THR) are to be performed for patients with ankylosing spondylitis. We have retrospectively reviewed 28 consecutive patients with ankylosing spondylitis who underwent both a spinal osteotomy and a THR from September 2004 to November 2012. In the cohort 22 patients had a spinal osteotomy before a THR (group 1), and six patients had a THR before a spinal osteotomy (group 2). The mean duration of follow-up was 3.5 years (2 to 9). The spinal sagittal Cobb angle of the vertebral osteotomy segment was corrected from a pre-operative kyphosis angle of 32.4 (SD 15.5°) to a post-operative lordosis 29.6 (SD 11.2°) (p < 0.001). Significant improvements in pain, function and range of movement were observed following THR. In group 2, two of six patients had an early anterior dislocation. The spinal osteotomy was performed two weeks after the THR. At follow-up, no hip has required revision in either group. Although this non-comparative study only involved a small number of patients, given our experience, we believe a spinal osteotomy should be performed prior to a THR, unless the deformity is so severe that the procedure cannot be performed.

Gapless magnetic and quasiparticle excitations due to the coexistence of antiferromagnetism and superconductivity in CeRhIn5: a study of 115In NQR under pressure.

We report systematic measurements of ac susceptibility, nuclear-quadrupole-resonance spectrum, and nuclear-spin-lattice-relaxation time (T1) on the pressure (P)-induced heavy-fermion superconductor CeRhIn5. The temperature (T) dependence of 1/T(1) at P=1.6 GPa has revealed that antiferromagnetism (AFM) and superconductivity (SC) coexist microscopically, exhibiting the respective transition at T(N)=2.8 K and T(MF)(c)=0.9 K. It is demonstrated that SC does not yield any trace of gap opening in low-lying excitations below T(onset)(c)=2 K, but T(MF)(c)=0.9 K, followed by a T(1)T=const law. These results point to the unconventional characteristics of SC coexisting with AFM. We highlight that both of the results deserve theoretical work on the gapless nature in the low-lying excitation spectrum due to the coexistence of AFM and SC and the lack of the mean-field regime below T(onset)(c)=2 K.

Coexistence of antiferromagnetism and superconductivity near the quantum criticality of the heavy-fermion compound CeRhIn5.

We report a study on the interplay between antiferromagnetism (AFM) and superconductivity (SC) in a heavy-fermion compound CeRhIn5 under pressure P=1.75 GPa. The onset of the magnetic order is evidenced from a clear split of 115In nuclear quadrupole resonance spectrum due to the spontaneous internal field below the Néel temperature T(N)=2.5 K. Simultaneously, bulk SC below T(c)=2.0 K is demonstrated by the observation of the Meissner diamagnetism signal whose size is the same as in the exclusively superconducting phase. These results indicate that the AFM coexists homogeneously with the SC at a microscopic level.

Evidence for unconventional strong-coupling superconductivity in PrOs4Sb12: an Sb nuclear quadrupole resonance study.

We report Sb-NQR results which evidence a heavy-fermion (HF) behavior and an unconventional superconducting (SC) property in Pr(Os4Sb12 with T(c)=1.85 K. The temperature (T) dependence of nuclear-spin-lattice-relaxation rate, 1/T(1), and NQR frequency unravel a low-lying crystal-electric-field splitting below T0 approximately 10 K, associated with Pr3+(4f(2))-derived ground state. In the SC state, 1/T(1) shows neither a coherence peak just below T(c) K nor a T3-like power-law behavior observed for anisotropic HF superconductors with the line-node gap. The isotropic energy gap with its size Delta/k(B)=4.8 K seems to open up across T(c) below T(*) approximately 2.3 K. It is surprising that Pr(Os4Sb12 looks like an isotropic HF superconductor-it may indeed argue for Cooper pairing via quadrupolar fluctuations.

Delocalized quasiparticles in the vortex state of an overdoped high-T(c) superconductor probed by 63Cu NMR.

We report the spin Knight shift (K(s)) and the nuclear spin-lattice relaxation rate (1/T1) in the vortex state as a function of magnetic field (H) up to 28 T in the high-Tc superconductor TlSr2CaCu2O6.8 (Tc = 68 K). At low temperatures well below Tc, both K(s) and 1/T1 measured around the middle point between the two nearest vortices (saddle point) increase substantially with increasing field, which indicate that the quasiparticle states with an ungapped spectrum are extended outside the vortex cores in a d-wave superconductor. The density of states (DOS) around the saddle point is found to be kappaN(0)square root[H/H(c2)], with kappa = 0.5-0.7 and N0 being the normal-state DOS.

Cytotoxic terpenoids and flavonoids from Artemisia annua.

The cytotoxic activity of nine terpenoids and flavonoids isolated from Artemisia annua was tested in vitro on several human tumor cell lines. These compounds are artemisinin, deoxyartemisinin, artemisinic acid, arteannuin-B, stigmasterol, friedelin, friedelan-3 beta-ol, artemetin, and quercetagetin 6,7,3',4'-tetramethyl ether. Friedelane-type triterpenoids were isolated for the first time from this plant. Artemisinin and quercetagetin 6,7,3',4'-tetramethyl ether showed significant cytotoxicity against P-388, A-549, HT-29, MCF-7, and KB tumor cells.

Synthesis of myristoyl CoA analogues and myristoyl peptides as inhibitors of myristoyl CoA:protein N-myristoyltransferase.

To develop inhibitors of myristoyl CoA:protein N-myristoyltransferase (NMT), a series of myristoyl coenzyme A analogues and myristoyl peptides were synthesized, including S-(2-oxopentadecyl)-CoA (1), S-(2-hydroxypentadecyl)-CoA (2), S-(2-oxopentadecyl)-pantetheine (3), Myr-N-Gly-(L)-Phe (4), Myr-N-Gly-(L)-Tyr (5), and Myr-N-Gly-(L)-Asn-Ala- Ala-Ser-Ala-Arg-(NH2) (6). Biological evaluation of these compounds in an in vitro NMT enzyme assay revealed that the nonhydrolyzable acyl CoA analogue 1 was the most potent inhibitor [inhibitor dissociation constant (Ki) = 24 nM]. A preliminary structure-activity relationship study showed that the adenosine moiety and the 2-keto group in this nonhydrolyzable analogue were necessary for inhibitory activity. A possible mechanism for the inhibition of NMT by 1 was proposed, in which 1 might block the reaction at the stage of an acyl-CoA-NMT-peptide complex. Product analogues such as the myristoylated peptides 4-6 were poor inhibitors of NMT.

Ohioensins and pallidisetins: novel cytotoxic agents from the moss Polytrichum pallidisetum.

Bioassay-directed fractionation of an EtOH extract of the moss Polytrichum pallidisetum (Polytrichaceae) led to the isolation of three novel benzonaphthoxanthenones, 1-O-methylohioensin B [6], 1-O-methyldihydroohioensin B [7] and 1,14-di-O-methyldihydroohioensin B [8], and two novel cinnamoyl bibenzyls, pallidisetin A [9] and pallidisetin B [10]. Their structures and relative stereochemistry were established by spectral analyses and chemical correlation. Compounds 6-10 exhibited cytotoxic activity against the human tumor cell lines RPMI-7951 melanoma and U-251 glioblastoma multiforme. These two types of compounds could hypothetically be derived from cinnamic acid and bibenzyls through different biogenetic pathways.

Chemoprevention of benzo[a]pyrene-induced forestomach cancer in mice by natural phthalides from celery seed oil.

Bioassay-directed fractionation of celery seed oil from the plant Apium graveolens (Umbelliferae) led to the isolation of five natural products, including d-limonene, p-mentha-2,8-dien-1-ol, p-mentha-8(9)-en-1,2-diol, 3-n-butyl phthalide, and sedanolide. Of these compounds p-mentha-2,8-dien-1-ol,3-n-butyl phthalide, and sedanolide exhibited high activities to induce the detoxifying enzyme glutathione S-transferase (GST) in the target tissues of female A/J mice. 3-n-Butyl phthalide and sedanolide (20 mg/dose every two days for a total of 3 doses) increased GST activity 4.5-5.9 and 3.2-5.2 times over the controls in the mouse liver and small intestinal mucosa, respectively. At the same dose, p-mentha-2,8-dien-1-ol induced GST activity about 3.7-fold above that of the controls. Thus, these compounds were further tested for their ability to inhibit benzo[a]pyrene- (BP) induced tumorigenesis in mice. After treatment with 3-n-butyl phthalide and sedanolide, the tumor incidence was reduced from 68% to 30% and 11%, respectively. About 67% and 83% reduction in tumor multiplicity was also observed with 3-n-butyl phthalide and sedanolide. p-Mentha-2,8-dien-1-ol produced only a small or no significant reduction of forestomach tumor formation. The data indicating that 3-n-butyl phthalide and sedanolide were both active in tumor inhibition and GST assays suggested a correlation between the inhibitory activity and the GST-inducing ability. The phthalides are known to determine the characteristic odor of celery. The results suggest that phthalides, as a class of bioactive natural products occurring in edible umbelliferous plants, may be effective chemopreventive agents.

Inhibition of benzo[a]pyrene-induced tumorigenesis by myristicin, a volatile aroma constituent of parsley leaf oil.

Glutathione S-transferase (GST) assay-guided fractionation of parsley leaf oil from the edible plant Petroselinum sativum Hoffm. (Umbelliferae) led to the isolation of myristicin. Myristicin showed high activity as an inducer of the detoxifying enzyme GST in the liver and small intestinal mucosa of female A/J mice. Reduction of myristicin yielded dihydromyristicin that retained the GST-inducing activity. Myristicin and dihydromyristicin were tested for their capacity to inhibit benzo[a]pyrene (B[a]P)-induced tumor formation in female A/J mice. A 65% inhibition of the tumor multiplicity in the lung was observed as the result of treatment of myristicin. Dihydromyristicin produced small or insignificant reduction of lung tumor formation. In the forestomach, myristicin showed a 31% inhibition of tumor formation; while dihydromyristicin exhibited a 27% inhibition. Comparison of the structures and activities indicated that the saturation of the isolated double bond in myristicin resulted in a significant decrease in the inhibitory activity against B[a]P-induced tumorigenesis. The present results showed that myristicin, an active inducer of GST activity, is an effective inhibitor of B[a]P-induced tumorigenesis in mice. Stimulation of GST activity by myristicin could be a major mechanism for its inhibition of B[a]P or other carcinogens that may be detoxified in the same manner. As a culinary herb parsley is regularly consumed by humans. Parsley leaf oil is also used extensively for garnishing and seasoning. The results of this study indicate that as a major volatile aroma constituent of parsley myristicin may be an effective cancer chemopreventive agent.

Isolation and biological evaluation of potential cancer chemopreventive agents from ambrette musk residue.

Two nitroaromatic compounds, 1-(1,1-dimethylethyl)-3,5-dimethyl-2,4-dinitrobenzene (1) and 1-[4-(1,1-dimethylethyl)-2,6-dimethyl-3,5-dinitrophenyl]ethanone or musk ketone (2), were isolated from ambrette musk residue, which is widely used in the food and cosmetics industry. The ability of 1 and 2 to induce increased activity of the detoxifying enzyme glutathione S-transferase was tested in A/J mice. Enzyme induction in the cytosols of liver, forestomach, lung, colon, and small intestinal mucosa was determined. Biological evaluation revealed that both compounds exhibit high activity as glutathione S-transferase inducers in liver and small intestinal mucosa. The effects of 1 and 2 on the levels of acid-soluble sulfhydryl in the five mouse tissues were also determined. Both compounds slightly elevated sulfhydryl levels in the small intestinal mucosa but significantly decreased the sulfhydryl levels in the other tissues. Because the ability of anticarcinogenic compounds to induce an increase in the detoxifying enzyme activity correlates with their tumor inhibitory activity, 1 and 2 may be potential cancer chemopreventive agents.

Anethofuran, carvone, and limonene: potential cancer chemopreventive agents from dill weed oil and caraway oil.

Bioassay-directed fractionation of dill weed oil and caraway oil, respectively, from the plants Anethum graveolens L. and Carum carvi L. (Umbelliferae) has led to the isolation of three monoterpenes, anethofuran (1), carvone (2), and limonene (3). Their structures were determined on the basis of spectral analysis. These compounds induced the detoxifying enzyme glutathione S-transferase in several mouse target tissues. The alpha,beta-unsaturated ketone system in carvone appeared to be critical for the high enzyme-inducing activity.

Sesquiterpenes from clove (Eugenia caryophyllata) as potential anticarcinogenic agents.

Bioassay-directed fractionation of clove terpenes from the plant Eugenia caryophyllata has led to the isolation of the following five active known compounds: beta-caryophyllene [1], beta-caryophyllene oxide [2], alpha-humulene [3], alpha-humulene epoxide I [4], and eugenol [5]. Their structures were determined on the basis of spectral analysis (hreims, 1H and 13C nmr). These compounds showed significant activity as inducers of the detoxifying enzyme glutathione S-transferase in the mouse liver and small intestine. The ability of natural anticarcinogens to induce detoxifying enzymes has been found to correlate with their activity in the inhibition of chemical carcinogenesis. Thus, these sesquiterpenes show promise as potential anticarcinogenic agents.

Phenylalkyl isothiocyanate-cysteine conjugates as glutathione S-transferase stimulating agents.

To develop analogues of phenylalkyl isothiocyanate with less toxicity and better biological activity, two water-soluble phenylalkyl isothiocyanate-cysteine conjugates, S-[N-benzyl(thiocarbamoyl)]-L-cysteine (1) and S-[N-(3-phenylpropyl)(thiocarbamoyl)]-L-cysteine (2), were synthesized. The induction of increased activity of the detoxifying enzyme glutathione S-transferase by the conjugates and their parent compounds was determined and compared in several tissues of A/J mice. The biological evaluation revealed that the conjugates as GST enzyme inducers appeared to be less toxic and even more potent than the parent compounds in the mouse bladder. Compounds 1 was much more active than 2 in all the tissues examined, while their parent compounds showed an inverse order of activity. Thus, an increase in the alkyl chain length of the parent isothiocyanates or a decrease in the alkyl length of the conjugates could result in higher enzyme-inducing activity in the same compound series. Since a number of nitrosamines have been identified as prime bladder carcinogens and phenylalkyl isothiocyanates have been reported to inhibit a wide range of carcinogenic nitrosamines, the corresponding conjugates may serve as prodrugs to protect against nitrosamine-induced urinary bladder carcinogenesis once they are delivered to the target organ.