Biomedical subjects

Y Shen

Publications and source records attributed to Y Shen.

At least 235 records · Page 13Linked to original sources

PubMed1999

Soluble amyloid beta peptide concentration as a predictor of synaptic change in Alzheimer's disease.

We have characterized amyloid beta peptide (Abeta) concentration, Abeta deposition, paired helical filament formation, cerebrovascular amyloid angiopathy, apolipoprotein E (ApoE) allotype, and synaptophysin concentration in entorhinal cortex and superior frontal gyrus of normal elderly control (ND) patients, Alzheimer's disease (AD) patients, and high pathology control (HPC) patients who meet pathological criteria for AD but show no synapse loss or overt antemortem symptoms of dementia. The measures of Abeta deposition, Abeta-immunoreactive plaques with and without cores, thioflavin histofluorescent plaques, and concentrations of insoluble Abeta, failed to distinguish HPC from AD patients and were poor correlates of synaptic change. By contrast, concentrations of soluble Abeta clearly distinguished HPC from AD patients and were a strong inverse correlate of synapse loss. Further investigation revealed that Abeta40, whether in soluble or insoluble form, was a particularly useful measure for classifying ND, HPC, and AD patients compared with Abeta42. Abeta40 is known to be elevated in cerebrovascular amyloid deposits, and Abeta40 (but not Abeta42) levels, cerebrovascular amyloid angiopathy, and ApoE4 allele frequency were all highly correlated with each other. Although paired helical filaments in the form of neurofibrillary tangles or a penumbra of neurites surrounding amyloid cores also distinguished HPC from AD patients, they were less robust predictors of synapse change compared with soluble Abeta, particularly soluble Abeta40. Previous experiments attempting to relate Abeta deposition to the neurodegeneration that underlies AD dementia may have failed because they assayed the classical, visible forms of the molecule, insoluble neuropil plaques, rather than the soluble, unseen forms of the molecule.

Aged↗

PubMed1999

601 octogenarians undergoing cardiac surgery: outcome and comparison with younger age groups.

BACKGROUND: Cardiac valve replacement and coronary artery bypass graft surgery (CABG) are being applied with increasing frequency in patients 80 years of age and older. METHODS: Six hundred one consecutive patients older than 80 years, undergoing cardiac surgery between 1976 and 1994 (CABG with saphenous vein graft, 329 [54.7%]; CABG with left internal mammary artery, 101 [16.8%]; CABG + valve, 80 [13.3%]; isolated aortic valve replacement, 71 [11.8%]; isolated mitral valve replacement, 18 [3.0%]), were studied retrospectively to assess short- and long-term survival. They were compared with 11,386 patients aged 60 to 69 years and 5,698 patients aged 70 to 79 years undergoing similar procedures during the same time interval. RESULTS: In comparison with patients 60 to 69 years old, more octogenarians were women (44.4% versus 25.6%, p<0.0001), had class IV angina (54.1% versus 38.9%, p<0.0001), and had congestive heart failure class IV (4.9% versus 3.0%, p = 0.0001). In-hospital death rates (9.1% versus 3.4%, p<0.0001) and stroke (5.7% versus 2.6%, p<0.0001) reflected these adverse clinical risk factors. However, Q-wave infarction tended to be less frequent (1.5% versus 2.6%, p = 0.102). Interestingly, hospital mortality (9.1% versus 6.7%, p = 0.028) was only slightly increased, and stroke (5.7% versus 4.7%, p = 0.286) was not more common in octogenarians than in patients 70 to 79 years old. Late-survival curves have similar slopes for the first 5 years in all clinical subgroups. However, after 5 years there is a more rapid decline in octogenarians than in younger age groups. Median 5-year survival was 55% for patients older than 80 years, 69% for patients 70 to 79 years, and 81% for patients 60 to 69 years old. CONCLUSIONS: When appropriately applied in selected octogenarians, cardiac surgery can be performed with acceptable mortality and excellent 5-year survival.

Aged↗

PubMed1999

Treatment of moderate mitral regurgitation and coronary disease by coronary bypass alone: late results.

BACKGROUND: In cases of moderate mitral regurgitation and coronary artery disease operative strategy continues to be debated between coronary artery bypass grafting alone and concomitant valve replacement or repair. We previously reported on 58 patients with moderate mitral regurgitation who had coronary artery bypass grafting between 1977 and 1983. We present the late results for this original cohort (test group), and a matched control group of coronary artery bypass grafting patients without mitral regurgitation (n = 58). METHODS AND RESULTS: In the original cohort, the hospital mortality rate was 3.4% (2 of 58), and 80.4% (45 of 56) of hospital survivors were alive at the time of initial follow-up (mean, 4.3+/-2.3 years). Hospital mortality in the control group was 6.9% (4 of 58 patients). Follow-up was 98.2% (108 of 110 patients) complete, with a mean follow-up time of 10.3+/-5.5 years. Kaplan-Meier curves for hospital survivors showed similar 5- and 10-year survival rates between the two groups (p = 0.59). On multivariate analysis, age 65 years or more, congestive heart failure class III or IV, and pulmonary capillary wedge pressure more than 17 mm Hg were significant (p < 0.05) independent predictors of diminished survival in the test group. CONCLUSIONS: Patients with moderate mitral regurgitation and coronary artery disease treated solely with coronary artery bypass grafting had acceptable early and late results. Moderate mitral regurgitation at the time of revascularization does not always warrant operative correction.

Aged↗

PubMed1999

Differential effect of chronic antidepressant treatments on lipopolysaccharide-induced depressive-like behavioural symptoms in the rat.

In the present study we observed that lipopolysaccharide (LPS) administration provoked a characteristic reduction in body weight gain, food consumption, saccharin (but not water) consumption and nocturnal locomotor activity. It has been previously suggested that the ability of LPS to suppress the consumption of, and preference for, a palatable solution such as saccharin without altering water consumption, may represent an anhedonic response. The results of the present study demonstrate that chronic treatment with the tricyclic antidepressant (TCA) desipramine (7.5 mg/kg; i.p.) prevented LPS-induced anorexia, loss of body weight, the antidipsogenic effect and hypoactivity. In contrast, chronic treatment with the antidepressants paroxetine (7.5 mg/kg; i.p.) and venlafaxine (10 mg/kg; i.p.) failed to alter any of the LPS-induced behavioural responses. Furthermore, chronic treatment with desipramine (and to a lesser extent paroxetine) reduced the consumption of, and preference for, saccharin suggesting that these antidepressant treatments induce an "anhedonic" response in their own right. In conclusion, chronic desipramine treatment attenuated LPS-induced depressive-like behavioural symptoms in the rat. However, chronic treatment with paroxetine and venlafaxine did not significantly alter LPS-induced behavioural responses. The results of the present study support the hypothesis that TCA's may exert part of their anti-depressive efficacy through their effects on the immune system. However, this property does not appear to be shared by newer antidepressants which possess a better side effect profile than the TCA's. The suppressive effect of TCA's on proinflammatory cytokine secretion is discussed as a mechanism by which these agents alter LPS-induced behavioural responses.

Adrenergic Uptake Inhibitors↗

PubMed1999

Modulation of desensitization at glutamate receptors in isolated crucian carp horizontal cells by concanavalin A, cyclothiazide, aniracetam and PEPA.

In horizontal cells freshly dissociated from crucian carp (Carassius auratus) retina, we examined the effects of modulators of glutamate receptor desensitization, concanavalin A, cyclothiazide, aniracetam and 4-[2-(phenylsulfonylamino)ethylthio]-2,6-difluoro-phenoxyacetam ide (PEPA), on responses to rapid application of glutamate and kainate, using whole-cell voltage-clamp techniques. Incubation of concanavalin A suppressed the peak response but weakly potentiated the equilibrium response of horizontal cells to glutamate. Cyclothiazide blocked glutamate-induced desensitization in a dose-dependent manner, which resulted in a steady increase of the equilibrium current. The concentration of cyclothiazide causing a half-maximal potentiation for the equilibrium response was 85 microM. Furthermore, cyclothiazide shifted the dose-response relationship of the equilibrium current to the right, but slightly suppressed the kainate-induced sustained current. These effects of concanavalin A and cyclothiazide are consistent with the supposition that glutamate receptors of carp horizontal cells may be an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)-preferring subtype. In order to further characterize the AMPA receptors of horizontal cells, modulation by aniracetam and PEPA of glutamate- and kainate-induced currents was studied. Aniracetam, a preferential modulator of flop variants of AMPA receptors, considerably blocked desensitization of glutamate-induced currents, but only slightly potentiated kainate-induced currents. It was further found that PEPA, a flop-preferring allosteric modulator of AMPA receptor desensitization, slightly suppressed the peak current, while it dramatically potentiated the equilibrium current induced by glutamate in a dose-dependent manner. PEPA was much potent than aniracetam at these receptors and showed the effect on glutamate-induced desensitization even at a concentration as low as 3 microM. PEPA also potentiated non-desensitizing currents induced by kainate, but with much less extent. These modulatory effects of concanavalin A, cyclothiazide, aniracetam and PEPA on AMPA receptors in carp horizontal cells were rather similar to those obtained at AMPA receptors assembled from flop variants expressed in Xenopus oocyte and HEK cell. Consequently, we speculate that the AMPA receptor on carp horizontal cells may predominantly carry the flop splice variants.

Animals↗

PubMed1999

Prior exposure to neurotrophins blocks inhibition of axonal regeneration by MAG and myelin via a cAMP-dependent mechanism.

MAG is a potent inhibitor of axonal regeneration. Here, inhibition by MAG, and myelin in general, is blocked if neurons are exposed to neurotrophins before encountering the inhibitor; priming cerebellar neurons with BDNF or GDNF, but not NGF, or priming DRG neurons with any of these neurotrophins blocks inhibition by MAG/myelin. Dibutyryl cAMP also overcomes inhibition by MAG/myelin, and cAMP is elevated by neurotrophins. A PKA inhibitor present during priming abrogates the block of inhibition. Finally, if neurons are exposed to MAG/myelin and neurotrophins simultaneously, but with the Gi protein inhibitor, inhibition is blocked. We suggest that priming neurons with particular neurotrophins elevates cAMP and activates PKA, which blocks subsequent inhibition of regeneration and that priming is required because MAG/myelin activates a Gi protein, which blocks increases in cAMP. This is important for encouraging axons to regrow in vivo.

Animals↗

PubMed1999

Parathyroid hormone stimulates cancellous bone formation at skeletal sites regardless of marrow composition in ovariectomized rats.

The purpose of the current report is to compare the skeletal effects of PTH treatment at red (hematopoietic) and yellow (fatty) marrow sites in ovariectomized (ovx) rats. In the first study, mature, slowly growing ovx rats that were 4 months of age and 4 weeks postovariectomy were treated with human parathyroid hormone [hPTH(1-34)] (80 microg/kg, 5 days/week) for 6 weeks. In the second study, aged ovx rats that were 15 months of age and 1 year postovariectomy were treated with PTH according to the same regimen for 10 weeks. The proximal tibial metaphysis (PTM) and first lumbar vertebra (LV), bone sites with red marrow, as well as the distal tibial metaphysis (DTM) and fifth caudal vertebra (CV), bone sites with yellow marrow, were processed undecalcified for quantitative bone histomorphometry. At the end of the first study in mature ovx rats, estrogen depletion induced a 73% loss of cancellous bone in the PTM and a 15% loss in the LV. In contrast, not even a trend for cancellous bone loss was observed in the DTM and CV of vehicle-treated ovx rats. PTH treatment of ovx rats increased cancellous bone volume by 191% in the PTM, 56% in the DTM, 47% in the LV, and 22% in the CV, compared with vehicle treatment of ovx rats. In addition, the hormone markedly increased cancellous bone formation by 177% in the PTM, 679% in the DTM, 309% in the LV, and 833% in the CV. Aged ovx rats (second study) exhibited moderate cancellous osteopenia in the LV but not the CV. PTH treatment increased cancellous bone volume by 67% and 37% and bone formation rate by 635% and 359% in the LV and CV, respectively, compared with vehicle treatment of ovx rats. Although the magnitude of the anabolic response to PTH may vary somewhat within the skeleton, the results indicate that PTH augments cancellous bone mass and markedly stimulates bone formation at skeletal sites, regardless of marrow composition.

Animals↗

PubMed1999

Assessing effects on long-term survival after early termination of randomized trials.

In this paper we present an approach to using historical control data to augment information from a randomized controlled clinical trial, when it is not possible to continue the control regimen to obtain the most reliable and valid assessment of long term treatment effects. Using an adjustment procedure to the historical control data, we investigate a method of estimating the long term survival function for the clinical trial control group and for evaluating the long term treatment effect. The suggested method is simple to interpret, and particularly motivated in clinical trial settings when ethical considerations preclude the long term follow-up of placebo controls. A simulation study reveals that the bias in parameter estimates that arises in the setting of group sequential monitoring will be attenuated when long term historical control information is used in the proposed manner. Data from the first and second National Wilms' Tumor studies are used to illustrate the method.

Bias↗

PubMed1999

Characterization of AMPA receptors on isolated amacrine-like cells in carp retina.

In amacrine-like cells freshly dissociated from crucian carp (Carassius auratus) retina, we recorded whole-cell responses to rapid application of glutamate and kainate. Currents induced by glutamate, but not kainate, usually showed extremely rapid desensitization, and the mean time constant for the decay of the responses to 10 mM glutamate was 2.77 ms. N-methyl-D-aspartate (NMDA) failed to induce any current even with coapplication of glycine and removal of extracellular Mg2 +. 1-(4-aminophenyl)-3-Methylcarbamyl-4-methyl-7,8-methylenedioxy-3, 4-dihydro-5H-2,3-benzodiazepine (GYKI 53655), a selective alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist, was found to completely block glutamate-induced currents, suggesting that the glutamate receptors on these cells are AMPA preferring. The value of EC50 for glutamate and kainate was determined to be 2.73 mM and 97.5 microM, respectively. Noise analysis of fluctuation of whole-cell currents induced by kainate of different concentrations indicated that the mean conductance of the AMPA receptor channels was 5.70 pS. Splice variant analysis of the AMPA receptors was also conducted by comparing the effects of cyclothiazide, a flip receptor-preferring modulator and 4-[2-(phenylsulphonylamino)ethylthio]-2,6-difluoro-phenoxyaceta mide (PEPA), a flop receptor-preferring modulator, on glutamate-induced responses. PEPA was much more potent than cyclothiazide at these receptors with a EC50 of 17.3 microM. The mean ratio of the potentiation by PEPA versus cyclothiazide (P/C ratio) was 4.39. These modulatory effects of cyclothiazide and PEPA were rather similar to those obtained at AMPA receptors assembled from flop variants expressed in Xenopus oocytes, suggesting that the AMPA receptor of the carp amacrine cells may predominantly consist of the flop splice variants.

Alternative Splicing↗

PubMed1999

Reduced expression of cyclooxygenase 2 proteins in hereditary nonpolyposis colorectal cancers relative to sporadic cancers.

BACKGROUND & AIMS: Cyclooxygenase (COX) enzymes catalyze the conversion of arachidonic acid to prostaglandins. Evidence suggests that nonsteroidal anti-inflammatory drugs reduce the risk of colorectal cancer (CRC) and that this effect is mediated through COX inhibition. We analyzed and compared expression of the inducible COX-2 isoform in colorectal neoplasms from patients with hereditary nonpolyposis colorectal cancer (HNPCC), familial adenomatous polyposis (FAP), and sporadic CRC. Given that COX-2 is induced by transforming growth factor (TGF)-beta and that TGF-beta type II receptor (RII) mutations are found in HNPCCs, we determined the relationship between RII status and COX-2 expression. METHODS: COX-2 protein expression was determined in colorectal epithelia using immunohistochemistry and Western blotting. Patients with HNPCC had known mutations in hMLH1 or hMSH2 genes and/or met the Amsterdam criteria. In CRCs from HNPCC cases, mutations were sought in the coding region of the RII gene using the polymerase chain reaction. RESULTS: COX-2 was detected in adenomas from 2 of 3 HNPCC, 6 of 7 FAP, and 5 of 8 sporadic cases. In CRCs, COX-2 staining was found in 16 of 24 (67%) HNPCC vs. 24 of 26 (92%) sporadic cases (P = 0.035) and in 2 of 2 FAP cases. Staining intensity was reduced in HNPCCs compared with sporadic CRCs (P = 0.035). Staining localized to the cytoplasm of neoplastic cells; normal epithelial cells were negative for COX-2. Overexpression of COX-2 in CRCs relative to normal mucosa was confirmed by Western blotting. TGF-beta RII mutations were detected in 12 of 14 HNPCCs examined, including 3 of 4 COX-2-negative and 9 of 10 COX-2-positive cancers. CONCLUSIONS: The frequency and intensity of COX-2 expression was significantly reduced in HNPCCs relative to sporadic CRCs, and was not a consequence of RII mutations. Given that many HNPCCs express COX-2, inhibition of this enzyme may be an important strategy to prevent CRC in these patients.

Adenomatous Polyposis Coli↗

PubMed1999

Focal adhesion targeting: the critical determinant of FAK regulation and substrate phosphorylation.

The focal adhesion kinase (FAK) is discretely localized to focal adhesions via its C-terminal focal adhesion-targeting (FAT) sequence. FAK is regulated by integrin-dependent cell adhesion and can regulate tyrosine phosphorylation of downstream substrates, like paxillin. By the use of a mutational strategy, the regions of FAK that are required for cell adhesion-dependent regulation and for inducing tyrosine phosphorylation of paxillin were determined. The results show that the FAT sequence was the single region of FAK that was required for each function. Furthermore, the FAT sequence of FAK was replaced with a focal adhesion-targeting sequence from vinculin, and the resulting chimera exhibited cell adhesion-dependent tyrosine phosphorylation and could induce paxillin phosphorylation like wild-type FAK. These results suggest that subcellular localization is the major determinant of FAK function.

Animals↗

PubMed1999

Statistical inference for self-designing clinical trials with a one-sided hypothesis.

In the process of monitoring clinical trials, it seems appealing to use the interim findings to determine whether the sample size originally planned will provide adequate power when the alternative hypothesis is true, and to adjust the sample size if necessary. In the present paper, we propose a flexible sequential monitoring method following the work of Fisher (1998), in which the maximum sample size does not have to be specified in advance. The final test statistic is constructed based on a weighted average of the sequentially collected data, where the weight function at each stage is determined by the observed data prior to that stage. Such a weight function is used to maintain the integrity of the variance of the final test statistic so that the overall type I error rate is preserved. Moreover, the weight function plays an implicit role in termination of a trial when a treatment difference exists. Finally, the design allows the trial to be stopped early when the efficacy result is sufficiently negative. Simulation studies confirm the performance of the method.

Biometry↗

PubMed1999

Confidence bands for cumulative incidence curves under the additive risk model.

In the context of competing risks, the cumulative incidence function is often used to summarize the cause-specific failure-time data. As an alternative to the proportional hazards model, the additive risk model is used to investigate covariate effects by specifying that the subject-specific hazard function is the sum of a baseline hazard function and a regression function of covariates. Based on such a formulation, we present an approach to constructing simultaneous confidence intervals for the cause-specific cumulative incidence function of patients with given risk factors. A melanoma data set is used for the purpose of illustration.

Adult↗

PubMed1999

Composition of toluene-degrading microbial communities from soil at different concentrations of toluene.

Toluene-degrading bacteria were isolated from hydrocarbon-contaminated soil by incubating liquid enrichment cultures and agar plate cultures in desiccators in which the vapor pressure of toluene was controlled by dilution with vacuum pump oil. Incubation in desiccators equilibrated with either 100, 10, or 1% (wt/wt) toluene in vacuum pump oil and testing for genomic cross-hybridization resulted in four genomically distinct strains (standards) capable of growth on toluene (strains Cstd1, Cstd2, Cstd5, and Cstd7). The optimal toluene concentrations for growth of these standards on plating media differed considerably. Cstd1 grew best in an atmosphere equilibrated with 0.1% (wt/wt) toluene, but Cstd5 failed to grow in this atmosphere. Conversely, Cstd5 grew well in the presence of 10% (wt/wt) toluene, which inhibited growth of Cstd1. 16S ribosomal DNA sequencing and cross-hybridization analysis indicated that both Cstd1 and Cstd5 are members of the genus Pseudomonas. An analysis of the microbial communities in soil samples that were incubated with 10% (wt/wt) toluene with reverse sample genome probing indicated that Pseudomonas strain Cstd5 was the dominant community member. However, incubation of soil samples with 0.1% (wt/wt) toluene resulted in a community that was dominated by Pseudomonas strain Q7, a toluene degrader that has been described previously (Y. Shen, L. G. Stehmeier, and G. Voordouw, Appl. Environ. Microbiol. 64:637-645, 1998). Q7 was not able to grow by itself in an atmosphere equilibrated with 0.1% (wt/wt) toluene but grew efficiently in coculture with Cstd1, suggesting that toluene or metabolic derivatives of toluene were transferred from Cstd1 to Q7.

Bacteria↗

PubMed1999

Bone and hormonal changes induced by skeletal unloading in the mature male rat.

To determine whether the rat hindlimb elevation model can be used to study the effects of spaceflight and loss of gravitational loading on bone in the adult animal, and to examine the effects of age on bone responsiveness to mechanical loading, we studied 6-mo-old rats subjected to hindlimb elevation for up to 5 wk. Loss of weight bearing in the adult induced a mild hypercalcemia, diminished serum 1,25-dihydroxyvitamin D, decreased vertebral bone mass, and blunted the otherwise normal increase in femoral mass associated with bone maturation. Unloading decreased osteoblast numbers and reduced periosteal and cancellous bone formation but had no effect on bone resorption. Mineralizing surface, mineral apposition rate, and bone formation rate decreased during unloading. Our results demonstrate the utility of the adult rat hindlimb elevation model as a means of simulating the loss of gravitational loading on the skeleton, and they show that the effects of nonweight bearing are prolonged and have a greater relative effect on bone formation in the adult than in the young growing animal.

Aging↗

PubMed1999

Chylomicron metabolism in an animal model for hyperlipoproteinemia type I.

Mink homozygous for the mutation Pro214Leu in lipoprotein lipase (LPL) had only traces of LPL activity but amounts of LPL protein in their tissues similar to those of normal mink. In normal mink, lymph chylomicrons from rats given [3H]retinol (incorporated into retinyl esters, providing a core label) and [14C]oleic acid (incorporated mainly in triglycerides (TG)) were rapidly cleared from the circulation. In the homozygous mink, clearance was much retarded. The ratio of TG to core label in plasma did not decrease and much less [14C]oleic acid appeared in plasma. Still, half of the labeled material disappeared from the circulating blood within 30;-40 min and the calculated total turnover of TG in the hypertriglyceridemic mink was almost as large as in normal mink. The core label was distributed to the same tissues in hypertriglyceridemic mink as in normal mink. Half to two-thirds of the cleared core label was in the liver. The large difference was that in the hypertriglyceridemic mink, TG label (about 40% of the total amount removed) followed the core label to the liver and there was no preferential uptake of TG over core label in adipose or muscle tissue. In normal mink, only small amounts of TG label (<10%) appeared in the liver, while most was in adipose and muscle tissues. Apolipoprotein B-48 dominated in the accumulated TG-rich lipoproteins in blood of hypertriglyceridemic mink, even in fasted animals.

Amino Acid Substitution↗

PubMed1999

Advances in photoacoustic noninvasive glucose testing.

We report here on in vitro and in vivo experiments that are intended to explore the feasibility of photoacoustic spectroscopy as a tool for the noninvasive measurement of blood glucose. The in vivo results from oral glucose tests on eight subjects showed good correlation with clinical measurements but indicated that physiological factors and person-to-person variability are important. In vitro measurements showed that the sensitivity of the glucose measurement is unaffected by the presence of common blood analytes but that there can be substantial shifts in baseline values. The results indicate the need for spectroscopic data to develop algorithms for the detection of glucose in the presence of other analytes.

Acoustics↗

PubMed1999

[Inhibin and ovarian cancer].

Previous observations from our laboratory have demonstrated that the levels of immunoreactive inhibin (ir-inh) are elevated in almost all patients with granulosa cell tumors and in the majority of postmenopausal women with mucinous ovarian cancers. The present report confirms these findings in a larger group of post-menopausal women. Immunohistochemistry for the inhibin alpha. beta A and beta B sununits shows predominantly epithelial staining in granulosa cell tumors and in the majority of mucinous cancers. Serous cystadenocarcinomas also frequently show positive staining. Studies seeking to identify G alpha i-2 or FSH receptor mutations have provided negative results in contrast to other reports. Further studies of the roles of the inhibin-related family of peptides in ovarian cancer diagnosis and monitoring are clearly indicated.

Adenocarcinoma, Mucinous↗