E-cadherin Expression in Canine Gastric Carcinomas: Association with Clinicopathological Parameters

E-cadherin (E-cad) is a cell-adhesion molecule known for its tumor-invasion suppressor function. E-cad expression was examined immunohistochemically in a series of canine tissue samples, including normal gastric mucosa (NGM; n = 3), gastric carcinomas (GC; n = 33), adjacent nonneoplastic mucosa (NNM; n = 32), neoplastic emboli (n = 16) and metastatic lesions (n = 9). The relationship between E-cad expression and clinicopathological features were investigated. In NGM, epithelial cells showed strong latero-lateral membranous expression of E-cad, and this pattern was considered normal. The membranous staining was preserved in all specimens of NNM (100%), whereas abnormal E-cad expression was found in 87.9% of the GCs. A marked difference in E-cad expression was observed between normal and malignant tissues (p < 0.0002). Abnormal E-cad expression was significantly more frequent in poorly/undifferentiated carcinomas (96%) and diffuse (95%) and indeterminate carcinomas (100%) than in well-differentiated/intestinal ones (62.5%; p = 0.0115 and p = 0.0392, respectively). There was significant association between abnormal E-cad expression and the depth of invasion (p = 0.0117), and the presence neoplastic emboli (p = 0.0194). No statistically significant differences in E-cad expression were observed concerning tumor location, histological type according to WHO classification, and presence of metastatic lesions. Therefore, deregulation of E-cad expression may play a role in canine gastric carcinogenesis and in tumor progression; moreover, it might be a prognostic tool for canine gastric cancer. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.Acknowledgments: A.R.F. (SFRH/BD/116373/2016) acknowledges FCT, the Portuguese Foundation for Science and Technology, for financial support. The authors of the research unit CECAV were also supported by the projects UIDB/CVT/00772/2020 and LA/P/0059/2020 funded by the Portuguese Foundation for Science and Technology (FCT). IPATIMUP integrates the i3S Research Unit, which is partially supported by FEDER through the Operational Programme for Competitiveness Factors-COMPETE and National Funds through the Portuguese Foundation for Science and Technology (FCT), under the project number PEst-C/SAU/LA0003/2013

Vimentin and Ki-67 immunolabeling in canine gastric carcinomas and their prognostic value

This study evaluated the expression of vimentin and Ki-67 proliferative index (PI) by immunohistochemistry in 30 canine gastric carcinomas (GCs) and a possible association with clinical and pathological features and patient’s survival time. Vimentin immunoreactivity was assessed in neoplastic cells (in primary lesions, emboli, and metastases) and tumor-associated stroma (TAS) of canine GCs. Ki-67 PI was quantified in the neoplastic epithelial component. Vimentin immunolabeling in neoplastic cells was found in 30% of the primary lesions, in 82% of the neoplastic emboli, and in 50% of the metastases; in TAS, it was observed in all cases. A mean of 16% of the TAS was immunolabeled for vimentin. High vimentin immunolabeling in the TAS (>16%) was detected in 40% of cases. The average value of Ki-67 PI was 50%, and 80% of the lesions had Ki-67 PI above 20%. Vimentin immunolabeling in neoplastic cells was more frequent in less-differentiated carcinomas (diffuse [29%] and indeterminate types [75%]) than well-differentiated carcinomas (intestinal type [0%], P = .049). No significant differences were observed in vimentin immunolabeling in the TAS or Ki-67 PI according to histological diagnosis, depth of invasion, presence of neoplastic emboli or metastases. However, vimentin immunolabeling in the TAS was positively correlated with Ki-67 PI (r = .394, P = .031). Furthermore, a moderate negative correlation was observed between Ki-67 PI and survival time (r = −0.540). Our results suggest that vimentin and Ki-67 PI have potential for providing prognostic information in cases of canine GCs

Immunoexpression of Trefoil Factor 1 in Non-Neoplastic and Neoplastic Canine Gastric Tissues

TFF1 expression is markedly reduced in human GCs, suggesting that TFF1 is a tumor suppressor for human gastric cancer. The present study evaluated the expression and distribution pattern of TFF1 in paraffin-embedded canine gastric tissue samples, including normal mucosa (n = 3), polyps (n = 8), carcinomas (n = 31) and their adjacent non-neoplastic mucosa (n = 30), neoplastic emboli (n = 14), and metastatic lesions (n = 9), by immunohistochemistry (IHC). All normal gastric tissues expressed TFF1 in the superficial foveolar epithelium and mucopeptic cells of the neck region. Most gastric polyps (GPs) displayed immunoreactivity for TFF1 in >75% of the epithelial component. In GCs, the expression of TFF1 was found reduced in 74.2% of the cases. The level of TFF1 expression had a decreased tendency from normal gastric mucosa to GPs and GCs (p 0.05). These findings suggest that TFF1 protein may play a role in canine gastric carcinogenesis, and further studies are necessary to define its usefulness as a prognostic indicator in canine gastric carcinoma.IPATIMUP integrates the i3S Research Unit, which is partially supported by FEDER through the Operational Programme for Competitiveness Factors-COMPETE and National Funds through the Portuguese Foundation for Science and Technology (FCT), under the project number PEst-C/SAU/LA0003/2013. A.R. Flores (SFRH/BD/116373/2016) acknowledges FCT, the Portuguese Foundation for Science and Technology, for financial support. The authors of the research unit CECAV also received funding from the project UIDB/CVT/0772/2020

Canine ovarian gonadoblastoma with dysgerminoma overgrowth: A case study and literature review

Background: Gonadoblastoma (GB) is a rare mixed germ cell-sex cord-stromal tumour, first described in humans, commonly found in dysgenetic gonads of intersex patients that have a Y chromosome. However, this entity in not recognized in the WHO classification of tumours of genital system of domestic animals. Herein, we describe a case of ovarian gonadoblastoma with proliferation of dysgerminoma and sex cord-stromal tumour components, in a phenotypically and cytogenetically normal bitch. Case presentation: A 17-year-old cross-breed bitch had a firm, grey-white multinodular mass in the left ovary. The tumour was submitted to histopathological examination and Y chromosome detected through karyotype analysis and PCR studies. Microscopically, the ovary was almost replaced by an irregular neoplasm composed of three distinct, intermixed elements: dysgerminoma, mixed germ cell-sex cord-stromal tumour resembling human GB and a proliferative sex cord-stromal tumour component. The germ cells of gonadoblastoma and dysgerminoma components were immunoreactive for c-KIT. Sex cord-stromal cells of gonadoblastoma were immunoreactive for a-inhibin. The sex cord-stromal tumour was immunoreactive for AE1/AE3, occasionally for a-inhibin and negative for epithelial membrane antigen (EMA). The karyotype was 78, XX and PCR analysis confirmed the absence of the Y chromosome. Conclusion: Based on these findings, a diagnosis of gonadoblastoma with proliferation of dysgerminoma and sex cord-stromal tumour was made. This is the first case of ovarian gonadoblastoma in a female dog.Ana R. Flores (SFRH/BD/116373/2016) and João Lobo (SFRH/BD/132751/2017) acknowledge FCT, the Portuguese Foundation for Science and Technology, for financial support. IPATIMUP integrates the i3S Research Unit, which is partially supported by FEDER through the Operational Programme for Competitiveness Factors-COMPETE and National Funds through the Portuguese Foundation for Science and Technology (FCT), under the project number PEst-C/SAU/LA0003/2013. We kindly thank Professor Beatriz Porto and Mrs. Cláudia Oliveira from laboratory of Cytogenetics of the ICBAS-UP for the karyotype analysis and Msc. Patrícia Barradas who provided PCR technical support. We would like to thank Paulo Flores for help with scientific illustration

Management of Septated Malignant Pleural Effusions

Purpose of Review: We review recent studies of patients with septated malignant pleural effusions, to understand what the clinical implications for patients are and what evidence-based methods should be used to manage these effusions. Recent Findings: Fibrinolytics improve effusion size assessed radiologically in patients with a chest drain inserted for septated malignant pleural effusions but this does not translate into an improvement in breathlessness relief or pleurodesis success. Fibrinolytics have also been used in patients with septated effusions associated with indwelling pleural catheters, but dyspnoea relief has not been assessed in this population. Patients with septated effusions or extensive adhesions appear to have a worse prognosis. Summary: Patients with septated malignant pleural effusions have a poor prognosis and do not gain clinical benefit from fibrinolytics via chest drain. The role of fibrinolytics for septated effusions associated with indwelling pleural catheters requires further study

Maharam-type kernel representation for operators with a trigonometric domination

[EN] Consider a linear and continuous operator T between Banach function spaces. We prove that under certain requirements an integral inequality for T is equivalent to a factorization of T through a specific kernel operator: in other words, the operator T has what we call a Maharam-type kernel representation. In the case that the inequality provides a domination involving trigonometric functions, a special factorization through the Fourier operator is given. We apply this result to study the problem that motivates the paper: the approximation of functions in L2[0, 1] by means of trigonometric series whose Fourier coefficients are given by weighted trigonometric integrals.This research has been supported by MTM2016-77054-C2-1-P (Ministerio de Economia, Industria y Competitividad, Spain).Sánchez Pérez, EA. (2017). Maharam-type kernel representation for operators with a trigonometric domination. Aequationes Mathematicae. 91(6):1073-1091. https://doi.org/10.1007/s00010-017-0507-6S10731091916Calabuig, J.M., Delgado, O., Sánchez Pérez, E.A.: Generalized perfect spaces. Indag. Math. 19(3), 359–378 (2008)Calabuig, J.M., Delgado, O., Sánchez Pérez, E.A.: Factorizing operators on Banach function spaces through spaces of multiplication operators. J. Math. Anal. Appl. 364, 88–103 (2010)Delgado, O., Sánchez Pérez, E.A.: Strong factorizations between couples of operators on Banach function spaces. J. Convex Anal. 20(3), 599–616 (2013)Dodds, P.G., Huijsmans, C.B., de Pagter, B.: Characterizations of conditional expectation type operators. Pacific J. Math. 141(1), 55–77 (1990)Flores, J., Hernández, F.L., Tradacete, P.: Domination problems for strictly singular operators and other related classes. Positivity 15(4), 595–616 (2011). 2011Fremlin, D.H.: Tensor products of Banach lattices. Math. Ann. 211, 87–106 (1974)Hu, G.: Weighted norm inequalities for bilinear Fourier multiplier operators. Math. Ineq. Appl. 18(4), 1409–1425 (2015)Halmos, P., Sunder, V.: Bounded Integral Operators on $$L^2$$ L 2 Spaces. Springer, Berlin (1978)Kantorovitch, L., Vulich, B.: Sur la représentation des opérations linéaires. Compositio Math. 5, 119–165 (1938)Kolwicz, P., Leśnik, K., Maligranda, L.: Pointwise multipliers of Calderón- Lozanovskii spaces. Math. Nachr. 286, 876–907 (2013)Kolwicz, P., Leśnik, K., Maligranda, L.: Pointwise products of some Banach function spaces and factorization. J. Funct. Anal. 266(2), 616–659 (2014)Kuo, W.-C., Labuschagne, C.C.A., Watson, B.A.: Conditional expectations on Riesz spaces. J. Math. Anal. Appl. 303, 509–521 (2005)Lindenstrauss, J., Tzafriri, L.: Classical Banach Spaces II. Springer, Berlin (1979)Maharam, D.: The representation of abstract integrals. Trans. Am. Math. Soc. 75, 154–184 (1953)Maharam, D.: On kernel representation of linear operators. Trans. Am. Math. Soc. 79, 229–255 (1955)Maligranda, L., Persson, L.E.: Generalized duality of some Banach function spaces. Indag. Math. 51, 323–338 (1989)Neugebauer, C.J.: Weighted norm inequalities for averaging operators of monotone functions. Publ. Mat. 35, 429–447 (1991)Okada, S., Ricker, W.J., Sánchez Pérez, E.A.: Optimal Domain and Integral Extension of Operators Acting in Function Spaces. Operator Theory: Adv. Appl., vol. 180. Birkhäuser, Basel (2008)Rota, G.C.: On the representation of averaging operators. Rend. Sem. Mat. Univ. Padova. 30, 52–64 (1960)Sánchez Pérez, E.A.: Factorization theorems for multiplication operators on Banach function spaces. Integr. Equ. Oper. Theory 80(1), 117–135 (2014)Schep, A.R.: Factorization of positive multilinear maps. Ill. J. Math. 28(4), 579–591 (1984)Schep, A.R.: Products and factors of Banach function spaces. Positivity 14(2), 301–319 (2010

Male circumcision and prevalence of genital human papillomavirus infection in men : a multinational study

Background: Accumulated evidence from epidemiological studies and more recently from randomized controlled trials suggests that male circumcision (MC) may substantially protect against genital HPV infection in men. The purpose of this study was to assess the association between MC and genital HPV infection in men in a large multinational study. Methods: A total of 4072 healthy men ages 18-70 years were enrolled in a study conducted in Brazil, Mexico, and the United States. Enrollment samples combining exfoliated cells from the coronal sulcus, glans penis, shaft, and scrotum were analyzed for the presence and genotyping of HPV DNA by PCR and linear array methods. Prevalence ratios (PR) were used to estimate associations between MC and HPV detection adjusting for potential confounders. Results: MC was not associated with overall prevalence of any HPV, oncogenic HPV types or unclassified HPV types. However, MC was negatively associated with non-oncogenic HPV infections (PR 0.85, 95% confident interval: 0.76-0.95), in particular for HPV types 11, 40, 61, 71, and 81. HPV 16, 51, 62, and 84 were the most frequently identified genotypes regardless of MC status. Conclusions: This study shows no overall association between MC and genital HPV infections in men, except for certain non-oncogenic HPV types for which a weak association was found. However, the lack of association with MC might be due to the lack of anatomic site specific HPV data, for example the glans penis, the area expected to be most likely protected by MC

Preparation and in vitro evaluation of 177Lu-iPSMA-RGD as a new heterobivalent radiopharmaceutical

This study aimed to synthesize a new 177Lu-iPSMA-RGD heterobivalent radiopharmaceutical, as well as to assess the in vitro radiopharmaceutical potential to target cancer cells overexpressing PSMA and a(v) b(3) integrins. The radiotracer prepared with a radiochemical purity of 98.8 ± 1.0% showed stability in human serum, specific recognition with suitable affinity to PSMA and a(v)b(3) integrins, and capability to inhibit cancer cell proliferation and VEGF signaling (antiangiogenic effect). Results warrant further preclinical studies to establish the 177Lu-iPSMA-RGD potential as a dual therapeutic radiopharmaceutical.CONACyT-CB-2016-01-28152

The secreted triose phosphate isomerase of Brugia malayi is required to sustain microfilaria production in vivo

Human lymphatic filariasis is a major tropical disease transmitted through mosquito vectors which take up microfilarial larvae from the blood of infected subjects. Microfilariae are produced by long-lived adult parasites, which also release a suite of excretory-secretory products that have recently been subject to in-depth proteomic analysis. Surprisingly, the most abundant secreted protein of adult Brugia malayi is triose phosphate isomerase (TPI), a glycolytic enzyme usually associated with the cytosol. We now show that while TPI is a prominent target of the antibody response to infection, there is little antibody-mediated inhibition of catalytic activity by polyclonal sera. We generated a panel of twenty-three anti-TPI monoclonal antibodies and found only two were able to block TPI enzymatic activity. Immunisation of jirds with B. malayi TPI, or mice with the homologous protein from the rodent filaria Litomosoides sigmodontis, failed to induce neutralising antibodies or protective immunity. In contrast, passive transfer of neutralising monoclonal antibody to mice prior to implantation with adult B. malayi resulted in 60–70% reductions in microfilarial levels in vivo and both oocyte and microfilarial production by individual adult females. The loss of fecundity was accompanied by reduced IFNγ expression by CD4+ T cells and a higher proportion of macrophages at the site of infection. Thus, enzymatically active TPI plays an important role in the transmission cycle of B. malayi filarial parasites and is identified as a potential target for immunological and pharmacological intervention against filarial infections

A p53-Dependent Response Limits Epidermal Stem Cell Functionality and Organismal Size in Mice with Short Telomeres

Telomere maintenance is essential to ensure proper size and function of organs with a high turnover. In particular, a dwarf phenotype as well as phenotypes associated to premature loss of tissue regeneration, including the skin (hair loss, hair graying, decreased wound healing), are found in mice deficient for telomerase, the enzyme responsible for maintaining telomere length. Coincidental with the appearance of these phenotypes, p53 is found activated in several tissues from these mice, where is thought to trigger cellular senescence and/or apoptotic responses. Here, we show that p53 abrogation rescues both the small size phenotype and restitutes the functionality of epidermal stem cells (ESC) of telomerase-deficient mice with dysfunctional telomeres. In particular, p53 ablation restores hair growth, skin renewal and wound healing responses upon mitogenic induction, as well as rescues ESCmobilization defects in vivo and defective ESC clonogenic activity in vitro. This recovery of ESC functions is accompanied by a downregulation of senescence markers and an increased proliferation in the skin and kidney of telomerase-deficient mice with critically short telomeres without changes in apoptosis rates. Together, these findings indicate the existence of a p53-dependent senescence response acting on stem/progenitor cells with dysfunctional telomeres that is actively limiting their contribution to tissue regeneration, thereby impinging on tissue fitness