Ahad Muhammadnejad

Multiple primary tumors (MPTs) are rare in dogs and challenging to diagnose when distinct lesions coexist. A 9‐year‐old mixed‐breed female presented with mammary and cutaneous masses. Imaging revealed no pulmonary metastasis but metallic foreign bodies. Histopathology identified a low‐grade intraductal carcinoma (HER2‐negative), melanosis with borderline proliferative features in an inguinal lymph node, and benign acrochordons. Immunohistochemistry confirmed S100 positivity and elevated Ki‐67 in the melanocytic component, suggesting melanocytic lesion with borderline proliferative features. Treatment included bilateral mastectomy, lymph node excision, and chemotherapy. Post‐treatment bloodwork showed mild cytopenias and biochemical changes consistent with hepatocellular stress. No recurrence or metastasis occurred within 6 months. This case highlights the role of multimodal diagnostics in distinguishing MPTs from metastasis and guiding therapy in complex geriatric oncology cases.

Clinical and molecular similarities between canine mammary tumors (CMTs) and human breast cancer (HBC) propel scientists to further study their application in comparative oncology as a model for human breast cancer. In total, 64 canine mammary tumors were selected to study the most common markers, which are applicable for human breast cancer treatment, including estrogen and progesterone receptors (ER and PR), human epidermal growth factor (HER2/neu), Ki67, and cyclooxygenase 2 (Cox2). Immunohistochemistry (IHC) was used to assess the protein expression. The Veterinary Nottingham Prognostic Index (Vet‐NPI) was also computed. Moreover, univariate and multivariable Cox proportional hazard analyses were applied to estimate hazard ratios (HRs). The results demonstrated that Ki67 was strongly expressed in the triple‐negative tumors, and Ki67 protein expression continuously increased over the increase of Cox2 protein expression (p < 0.001). Further analysis revealed a significant difference among canine mammary subtypes and Vet‐NPI, in which triple‐negative tumors displayed the highest mean score compared to other subtypes (p < 0.001). In addition, the multivariable analysis revealed that the regional mastectomy procedure (adjusted HR = 2.78 (1.14–6.8)), the triple‐negative tumors (adjusted HR = 48.08 (7.74–298.8)), strong Ki67 protein expression group (adjusted HR = 7.88 (2.02–30.68)), and strong Cox2 protein expression group (adjusted HR = 29.35 (5.18–166.4)) demonstrated significantly lower disease‐free survival rates compared to other corresponding groups. Overall, canine mammary tumors showed strong similarities to human breast cancer in terms of clinical and molecular aspects; therefore, they could be suggested as a model for human breast cancer in comparative oncology.

Introduction: Lung cancer is an important burden, causing a massive rate of deaths every year. Using a specialized treatment regimen can improve treatment outcomes and reduce treatment-related adverse events. This study aimed to evaluate the protective effects of the Opuntia dillenii fruit hydroalcoholic extract (ODHAE) in a mouse model of lung cancer. Methods: Eight groups of lung cancer-induced BALB/c mice (each containing twelve animals) were included in this study. They were the control group, groups receiving the ODHAE extract at doses of 50, 100, and 200 mg/kg by oral gavage, the cisplatin group receiving cisplatin intraperitoneal injection, and groups receiving cisplatin and different doses of ODHAE (50, 100, and 200 mg/kg). Weight and tumor changes were evaluated in the short and long phases of the study, including 30 and 90 days, respectively. Liver transaminase and survival time were evaluated in different groups. Malondialdehyde (MDA) was evaluated in different groups as an indicator of lipid peroxidation. Statistical tests were performed using GraphPad Prism 8. Graphs were designed using GraphPad Prism 8 as well. Results: The observed weight changes were not statistically significant across all groups, except for group 8. However, in groups that did not receive cisplatin treatment, there was a significant increase in tumor volume. Conversely, tumor volume change did not reach statistical significance in all groups receiving cisplatin. The administration of ODHAE, along with cisplatin, demonstrated a dose-dependent increase in the survival time among the relevant groups. Furthermore, oral administration of ODHAE exhibited a significant reduction in transaminase levels, serving as a reliable biomarker for assessing the hepatoprotective effect of the ODHAE extract. Additionally, ODHAE displayed a dose-dependent reduction in MDA levels, indicating its potential as a therapeutic agent for mitigating oxidative stress. Conclusion: The administration of ODHAE was not effective in reducing tumor growth but significantly increased survival time and healed the liver injury induced by cisplatin.

Background and Objective: The platelet-derived growth factor receptor (PDGFR) signaling pathway has a vital function as a regulator of glioma development. PDGFRA alterations have been observed in a variety of cancers and have been important clinical targets for tyrosine kinase inhibitors like Imatinib. The aim of this study was to evaluate the role of ...

Background: Up-regulation of ribosome biogenesis encodes the factors related to carcinogenesis. It has been shown that the nucleus diameter and number of nucleoli increase from normal mucosa to oral squamous cell carcinoma (OSCC). The relationship between nuclear parameters and lymph node involvement in OSCC has not been established, yet. The aim of this study was to evaluate the nuclear parameters comprising nucleoli count and nucleus: nucleoli ratio in relation to regional lymph node involvement in OSCC. Methods: Thirty-four formalin-fixed, paraffin embedded sections from different histopathologic grades of OSCC were stained with methyl green-pyronin. Mean number of nucleoli and nucleus: nucleoli ratio were calculated in 100 tumor cells from 10 random selected fields and compared based on lymph node involvement. Results: Nucleoli count in cases with metastasis to regional lymph nodes was not significantly different from that in cases without regional lymph nodes involvement (P=0.29). The difference of nucleus: nucleoli ratio in cases with and without lymph nodes involvement were not significant (P=0.52). No significant correlation was found between the nucleoli count and lymph node involvement (r=0.08, P=0.78). The correlation between nucleus: nucleoli ratio and lymph node involvement was significant (r=0.58, P=0.02). Conclusion: The nucleus: nucleoli ratio of tumoral cells in OSCC was correlated to lymph node involvement. Based on the results, nucleus: nucleoli ratio can potentially be a useful tool to determine the lymph node involvement in OSCC.

Purpose: Triple-negative breast cancer (TNBC) is specified by high vascularity and repetitious metastasis. Although several studies have indicated that angiogenesis has an important role in invasive breast cancer, a suitable model of TNBC that can show the exact onset of angiogenesis factors still needs to be developed. The purpose of this study is to determine the expression level of angiogenesis factors in different clinical stages of the 4T1 tumor as TNBC mouse model. Methods: Twenty mice were injected by the 4T1 cell line, and four mice selected as healthy controls. Following by tumor induction, the mice were randomly put into four groups, each contains four mice. Once the tumor volume reached to the early stage (500 mm3 ), they were removed by surgery. Then, the expression levels of Hif1α, VEGFR1, and VEGFR2 genes, as well as tumor markers of VEGF, bFGF and CD31, were evaluated by qPCR and immunohistochemistry (IHC) respectively. The statistical analysis was done by SPSS version 16. Results: TNBC tumors were confirmed and multi-foci metastasis in the lung were seen. The mRNA and protein expression levels of the angiogenesis factors increased in the early stage and as the tumor grew, their expression level enhanced dramatically. Conclusion: The 4T1 syngeneic mouse tumor may serve as an appropriate TNBC model for further investigation of the angiogenesis and therapies. Moreover, angiogenesis factors are induced before the advanced stage, and anti-angiogenesis therapy is necessary to be considered at the first line of treatment in TBNC.

Canine malignant mammary gland tumors (CMMGTs) are the most common malignancies observed in females. Several biological similarities have been reported between CMMGTs and human breast cancer (HBC). The present study aimed to assess the correlation of vimentin filaments overexpression, as part of the process of epithelial‑mesenchymal transition (EMT) and the clinicopathological characteristics in CMMGTs. The clinicopathological characteristics of 42 CMMGTs were collected. Paraffin‑embedded blocks underwent immunohistochemistry staining, which was performed using vimentin (to assess the evolution of the EMT process), Ki‑67 (for evaluation of tumor proliferation) and cluster of differentiation 34 (CD34) (for evaluation of angiogenesis) antibodies. The tumor stage, grade, vascular invasion, margin status, rate of expression of the vimentin filaments, microvessel density‑CD34 and proliferation rate data were obtained. Finally, the association between the expression of the vimentin filaments and those parameters was resolved statistically. A significant association was shown between the overexpression of the vimentin filaments and tumor size (r=0.71, P=0.03), tumor grade (r=0.80, P=0.021), angiogenesis (r=0.57, P=0.043), proliferation coefficient (r=0.06, P=0.001) and vascular invasion (r=0.76, P=0.043). Vimentin overexpression did not statistically correlate with the tumor stage or the margin status. Similar to the findings of the present study, certain recent studies have indicated that vimentin filament expression in HBC and CMMGTs is associated with the severity of cancer. Thus, spontaneous canine mammary tumor models appear to be an appropriate animal model for breast cancer research, and the results of the present study could aid to reinforce the association.

Overexpression of HER-2/neu in Malignant Mammary Tumors: Translation of Clinicopathological Features from Dog to Human Canine mammary gland tumors;human breast cancer;HER-2/neu gene; Background: Canine mammary gland tumors (CMGTs) are the most common tumor found in bitches. Changes in HER-2/neu genes in human breast cancer (HBC) lead to decrease in disease-free survival (DFS) and overall survival rate (OSR). Previous studies have demonstrated that the biological behavior of malignant mammary gland tumors (MMGTs) is similar to that of HBC. The present study aimed at evaluating the relationship between overexpression of HER-2/neu and clinicopathological features in MMGTs to represent a model of prognostic factors for HBC. Materials and Method: The clinicopathological data of 35 MMGTs were obtained. Immunohistochemical staining with HER-2, Ki-67 and CD34 markers was conducted with sections from paraffin-embedded blocks. According to standard protocols, histological type, grade, margin status, lymphovascular invasion (LVI), HER-2/neu score, proliferation rate and microvessel density (MVD) of tumors were determined and the association of HER-2/neu overexpression with these parameters was assessed statistically. Results: The IHC results showed that 12 (34.3%) cases were HER-2/neu positive. Statistical analyses indicated a significant relationship between HER-2 positivity and tumor grade (p=0.043), which also was demonstrated with cancer stage (p=0.035), tumor margin involvement (p=0.016), proliferation index (p=0.001) and MVD (p=0.001); however, there was no statistical relationship between LVI and tumor size. Overexpression of the HER-2/neu gene in MMGTs results in similar biological behavior as that of HBC; as a result, these tumors have can be considered to have important similarities in clinicopathological characteristics. Conclusions: MMGTs can be regarded as an HBC animal model. Further studies in this field would result in new treatments that could be beneficial for both dogs and humans.