Thymidine Phosphorylase Expression and Microvascular Density Correlation Analysis in Canine Mammary Tumor: Possible Prognostic Factor in Breast Cancer

Zizzo, Nicola; Passantino, Giuseppe; D'alessio, Roberta Maria; Tinelli, Andrea; Lopresti, G.; Patruno, Rosa; Tricarico, Domenico; Maqoud, Fatima; Scala, Rosa; Zito, Francesco Alfredo; Ranieri, Girolamo

doi:10.3389/fvets.2019.00368

Cited by 17 publications

(21 citation statements)

References 50 publications

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“…Poor patient outcomes observed in advanced-stage patients despite elevated levels of TYMP may be attributed to the dual role of TYMP in promoting angiogenesis and metastasis, aside from its role in 5-FU metabolism [ 222 , 231 ]. Such discrepancy may be the result of contrasting treatment regimens between primary and metastatic tumors as the administration of oxaliplatin, irinotecan, and capecitabine alongside 5-FU may provoke TYMP expression [ 248 , 249 ].…”

Section: Mechanism Of Resistance By Key 5-fluorouracil Enzymesmentioning

confidence: 99%

Recent Updates on Mechanisms of Resistance to 5-Fluorouracil and Reversal Strategies in Colon Cancer Treatment

Azwar

Seow

Abdullah

et al. 2021

Biology

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5-Fluorouracil (5-FU) plus leucovorin (LV) remain as the mainstay standard adjuvant chemotherapy treatment for early stage colon cancer, and the preferred first-line option for metastatic colon cancer patients in combination with oxaliplatin in FOLFOX, or irinotecan in FOLFIRI regimens. Despite treatment success to a certain extent, the incidence of chemotherapy failure attributed to chemotherapy resistance is still reported in many patients. This resistance, which can be defined by tumor tolerance against chemotherapy, either intrinsic or acquired, is primarily driven by the dysregulation of various components in distinct pathways. In recent years, it has been established that the incidence of 5-FU resistance, akin to multidrug resistance, can be attributed to the alterations in drug transport, evasion of apoptosis, changes in the cell cycle and DNA-damage repair machinery, regulation of autophagy, epithelial-to-mesenchymal transition, cancer stem cell involvement, tumor microenvironment interactions, miRNA dysregulations, epigenetic alterations, as well as redox imbalances. Certain resistance mechanisms that are 5-FU-specific have also been ascertained to include the upregulation of thymidylate synthase, dihydropyrimidine dehydrogenase, methylenetetrahydrofolate reductase, and the downregulation of thymidine phosphorylase. Indeed, the successful modulation of these mechanisms have been the game plan of numerous studies that had employed small molecule inhibitors, plant-based small molecules, and non-coding RNA regulators to effectively reverse 5-FU resistance in colon cancer cells. It is hoped that these studies would provide fundamental knowledge to further our understanding prior developing novel drugs in the near future that would synergistically work with 5-FU to potentiate its antitumor effects and improve the patient’s overall survival.

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Section: Mechanism Of Resistance By Key 5-fluorouracil Enzymesmentioning

confidence: 99%

Recent Updates on Mechanisms of Resistance to 5-Fluorouracil and Reversal Strategies in Colon Cancer Treatment

Azwar

Seow

Abdullah

et al. 2021

Biology

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“…The blocked sections were incubated overnight at 48°C anti-mouse primary antibodies for NFκB p50 (E-10): sc-8414; MAFbx (F-9): sc-166806; caspase-3 (E-8): sc-7272; BNIP-3 (ANa40): sc-56167 (Santa Cruz Biotechnology, Inc.) diluted 1/100 for 40 min then thoroughly washed in 0.05 M buffered with Tris saline (pH 7.6) and incubated with streptavidinperoxidase (Dako, 1: 100) for 40 min. 3, 3-diaminobenzidine (DAB) (Dako Glostrup, Denmark) was used as the chromogen; to counteract the core of Gill'S hematoxylin (Polysciences, Warrington, PA) after sections have been dehydrated and assembled (Zizzo et al, 2019). Experiments were performed by an investigator blinded to mouse genotype.…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…The percentage of KATP current inhibition induced by glibenclamide (Glib) was calculated as -(I CTRL-I drug)/(I CTRL-I leak) x 100, where I leak was the current recorded after the application of 5 × 10 −3 M MgATP on skeletal muscle fibers. The frequency of myofibers positivity was calculated on 50 cells per section (Zizzo et al, 2019).…”

Section: Data Analysis and Statisticsmentioning

confidence: 99%

Pathophysiological Consequences of KATP Channel Overactivity and Pharmacological Response to Glibenclamide in Skeletal Muscle of a Murine Model of Cantù Syndrome

et al. 2020

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Cantù syndrome (CS) arises from mutations in ABCC9 and KCNJ8 genes that lead to gain of function (GOF) of ATP-sensitive potassium (KATP) channels containing SUR2A and Kir6.1 subunits, respectively, of KATP channels. Pathological consequences of CS have been reported for cardiac and smooth muscle cells but consequences in skeletal muscle are unknown. Children with CS show muscle hypotonia and adult manifest fatigability. We analyzed muscle properties of Kir6.1[V65M] CS mice, by measurements of forelimb strength and ultrasonography of hind-limb muscles, as well as assessing KATP channel properties in native Flexor digitorum brevis (FDB) and Soleus (SOL) fibers by the patch-clamp technique in parallel with histopathological, immunohistochemical and Polymerase Chain Reaction (PCR) analysis. Forelimb strength was lower in Kir6.1wt/VM mice than in WT mice. Also, a significant enhancement of echodensity was observed in hind-limb muscles of Kir6.1wt/VM mice relative to WT, suggesting the presence of fibrous tissue. There was a higher KATP channel current amplitude in Kir6.1wt/VM FDB fibers relative to WT and a reduced response to glibenclamide. The IC50 of glibenclamide to block KATP channels in FDB fibers was 1.3 ± 0.2 × 10−7 M in WT and 1.2 ± 0.1 × 10−6 M in Kir6.1wt/VM mice, respectively; and it was 1.2 ± 0.4 × 10−7 M in SOL WT fibers but not measurable in Kir6.1wt/VM fibers. The sensitivity of the KATP channel to MgATP was not modified in Kir6.1wt/VM fibers. Histopathological/immunohistochemical analysis of SOL revealed degeneration plus regressive-necrotic lesions with regeneration, and up-regulation of Atrogin-1, MuRF1, and BNIP3 mRNA/proteins in Kir6.1wt/VM mice. Kir6.1wt/VM mutation in skeletal muscle leads to changes of the KATP channel response to glibenclamide in FDB and SOL fibers, and it is associated with histopathological and gene expression changes in slow-twitch muscle, suggesting marked atrophy and autophagy.

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“…Rodents, including rats, have been treated as disposable pets because of their small size and low cost. Several studies describe the characteristics of these models and their importance to the human disease to study a variety of aspects of breast cancer biology (Zizzo et al 2019;Zeng et al 2020).…”

Section: Case Description and Discussionmentioning

confidence: 99%

Surgical, histological, and immunohistochemical approach to spontaneous malignant mammary tumor in a fancy rat (Rattus norvegicus domestica): a case report

et al. 2021

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A domestic rat (Rattus norvegicus domestica) was presented to the Department of Veterinary Medicine of the University of Bari “Aldo Moro” (Bari, Italy) for the presence of a progressive growing unilateral mass. The mass was completely surgically removed, and then histologically and immohistochemically evaluated. The lesion was diagnosed as mammary ductal carcinoma based on histopathological examination. Immunohistochemistry staining for estrogen receptor alpha (ERα) and proliferation marker Ki-67 were found to be positive. The rat was rechecked 3 months thereafter, with total body radiographs taken for metastatic assessment, and no macroscopic evidence of tumor recurrence was observed at the surgical site. Thus, the most effective weapon remains prevention, so owners should be advised to timely spay their pets to reduce the probability of mammary tumor appearance.

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Thymidine Phosphorylase Expression and Microvascular Density Correlation Analysis in Canine Mammary Tumor: Possible Prognostic Factor in Breast Cancer

Cited by 17 publications

References 50 publications

Recent Updates on Mechanisms of Resistance to 5-Fluorouracil and Reversal Strategies in Colon Cancer Treatment

Recent Updates on Mechanisms of Resistance to 5-Fluorouracil and Reversal Strategies in Colon Cancer Treatment

Pathophysiological Consequences of KATP Channel Overactivity and Pharmacological Response to Glibenclamide in Skeletal Muscle of a Murine Model of Cantù Syndrome

Surgical, histological, and immunohistochemical approach to spontaneous malignant mammary tumor in a fancy rat (Rattus norvegicus domestica): a case report

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