Inflammatory Mammary Carcinoma Research Articles

Tetramethylpyrazine-Rhein Derivative inhibits the migration of canine inflammatory mammary carcinoma cells by mitochondrial damage-mediated apoptosis and cadherins downregulation

BackgroundCanine inflammatory mammary carcinoma (CIMC) has a high incidence of metastasis, high lethality, and poor prognosis, which needs novel adjuvant agents. Tetramethylpyrazine-Rhein Derivative (TRD) has been shown to have antitumor activity, which is a potential research direction for CIMC. PurposeThis study evaluated the efficacy of TRD on CIMC in vitro and in vivo, and provided possibilities for the application of active compounds in traditional Chinese medicine. MethodsIn vitro, TRD cytotoxicity was measured with CCK-8. Flow cytometry and transmission electron microscope were used to detect the cell cycle, cell death, and changes in mitochondria. Wound-healing assay, cell invasion assay, and scanning electron microscope were used to evaluate the suppression of cell migration and invasion. Expression changes were detected by RT-qPCR and western blot assay. In vivo, the lung metastasis models were randomly divided into control, low-dose TRD, high-dose TRD, and positive groups. Each group was administered orally once a day for 18 days and took in vivo imaging photos. ResultsThe IC50 of TRD in CHMp and MDCK were 42.59 and 79.37 μM, respectively. TRD mediated cell apoptosis by mitochondrial damage and caused S and G2/M phase arrest by downregulating cyclin B1. Moreover, TRD reduced filopodia and inhibited cell migration by downregulating cadherins. In CIMC lung metastasis models, TRD could effectively inhibit tumor growth (P < 0.001) in the lungs without significant toxicity. ConclusionTRD showed potential activity to inhibit CIMC lung metastasis with multi-target and low toxicity.

Establishment of stable expression of firefly luciferase and EGFP in a canine inflammatory mammary carcinoma cell line and tumor-bearing model in nude mice.

Canine inflammatory mammary carcinoma (CIMC) is a type of canine malignant mammary tumor with a poor prognosis and high mortality. We transduced firefly luciferase and enhanced green fluorescent protein (EGFP) into CHMp, a CIMC cell line, and established CHMp-Luc-EGFP cells. We investigated the characteristics of this cell line in vitro and in vivo. CHMp-Luc-EGFP was passaged continuously 75 times, with stable expression of luciferase and EGFP. Compared with the wild-type, CHMp-Luc-EGFP had similar proliferation, metastasis, histopathology characteristics, and expression of E-cadherin, N-cadherin, and Ki-67. A tumor-bearing model was established by implantation of CHMp-Luc-EGFP cells, and the dynamic changes of tumors were visualized and quantified using the IVIS imaging system. In summary, the cell line we established could reflect the biological characteristics of CHMp cells, visualize the tumor progression in vivo, and provide a powerful tool for the study of CIMC.

Establishment of a New Canine Inflammatory Mammary Carcinoma Cell Line and Analysis of its Cystine-glutamate Transporter Subunit Expression.

IntroductionInflammatory mammary carcinoma (IMC) is a rare disease with a poor prognosis and one affecting dogs. Inflammatory breast carcinoma (IBC) is a subtype of malignant breast cancer in humans with a high degree of malignancy and a similarly poor prognosis. Since the clinical symptoms and prognoses of both are similar, canine IMC has been considered as a model of human IBC. In this study, we newly established a stable IMC-derived cell line from a patient at the Yamaguchi University Animal Medical Center in Japan.Material and MethodsThe patient was a female toy poodle presenting with an inflamed mammary gland, which was diagnosed as IMC. The cell line was established from a tissue biopsy. Surface antigen marker (CD24 and CD44) expression was determined. Cystine/glutamate antiporter (xCT) expression was determined by Western blotting, flow cytometry and fluorescence immunostaining, and sulfasalazine was administered to ascertain if it suppressed xCT expression. Stem cell marker (Nanog, Sox2, Myc and Klf4) expression and aldehyde dehydrogenase (ALDH) activity were also investigated.ResultsThe cultured cells showed xCT, and its suppression showed downregulation of stem cell markers and ALDH activity. Stable cell proliferation was verified.ConclusionA new canine IMC-derived cell line was established. In the future, we aim to study the effect of xCT on the maintenance of cancer stem cell properties in canine tumours, and propose a new therapeutic method for the treatment of canine IMC by targeting xCT.

Factors related to the suppression of the antitumour immune response in female dogs with inflammatory mammary carcinoma

Inflammatory mammary carcinoma (IMC), a neoplasia affecting women and female dogs, is considered an aggressive cancer with high metastatic potential and a low survival rate. Studies focused on the tumour microenvironment indicate that the aggressive behaviour of this tumour is primarily correlated with immunological factors as well as inflammation. The objective of this study was to analyse the possible strategies used by the tumour cells to suppress the immune response in female dogs with IMC. Forty-six female dogs were divided into three groups: control (C, n = 10), IMC (n = 14) and mammary carcinoma (MC, n = 22). Clinical-pathological evaluations, survival at follow-up, immunophenotyping of leukocytes in peripheral blood and tumours, and immunohistochemical evaluation of CD4+, granzyme B, perforin and FAS-L were performed. Clinical and pathological results showed a higher frequency of the primary form of neoplasia, solid arrays of tumor cells and a lower survival rate in the IMC group (30 days). Morphometric analysis of inflammatory infiltrate revealed more lymphocytes and macrophages in the IMC group. Immunophenotyping analysis of peripheral blood revealed a higher frequency of CD8+ T-cells (p = 0.0017), a lower frequency of CD4+ T-cells (p <0.0001), and significantly higher mean MHCI and MHCII CD14+ fluorescence intensity in the IMC group (p = 0.038 and p = 0.0117, respectively). The immunohistochemical evaluation of tumour sections showed fewer FAS-L-positive inflammatory cells in the IMC group. These results suggest the important contribution of CD8+ T-cells, macrophages and FAS-L in the aggressiveness of IMC.

Adenosquamous inflammatory mammary carcinoma in bitch: Can CA 15-3, CRP and LDH improve prognosis?

Inflammatory mammary carcinoma (IMC) is characterized by the presence of any subtype of aggressive carcinoma in association with an intense inflammatory reaction, in addition to the presence of tumor emboli. Considering IMC as a type of cancer with chronic inflammation, the complex relationship between inflammation, and alterations in cellular metabolism have highlighted the rationale assessment of cancer antigen 15-3 (CA 15-3), c-reactive protein (CRP), and lactate dehydrogenase (LDH). The present report had the objective to describe a rare case of adenosquamous carcinoma in mammary gland of a 10-year-old bitch, 7 kg, sexually intact, mixed-breed and how CA 15-3, CRP and LHD helped to determinate the clinical presentation of inflammatory carcinoma and the prognosis. Complete clinical staging, cell blood count and renal, and hepatic biochemistry was performed and did not reveal any significant abnormalities. CA 15-3 (9.46 IU/mL), CRP (5.3 mg/L), and LDH (287 U/L) were all above the references values reported by the literature. Although adenosquamous carcinoma of the mammary gland with inflammatory presentation in dogs is rare, the association of serum biomarkers could improve the patient's prognosis evaluation.

Pathological Studies on Inflammatory Mammary Cystic Papillary Adenocarcinoma in a Male Dog

Inflammatory mammary carcinoma (IMC) is a rare and aggressive type of malignant mammary tumour. An 11-year-old intact male non-descript dog was presented to Madras Veterinary College Teaching Hospital with the history of painful swelling on the ventral abdomen for the past one week. Clinical examination revealed dehydration, sunken eyeballs, unilateral hindlimb edema and pain on palpation. Hematobiochemical studies revealed increase in serum alkaline phosphatase, blood urea nitrogen and creatinine levels. Cytological examination of fine needle aspirate biopsy revealed numerous lymphocytes and erythrocytes with small clusters of atypical cells with anisokaryosis with abundant cytoplasm. The dog collapsed during the treatment and the carcass was submitted to the Department of Veterinary Pathology for necropsy. Detailed necropsy examination revealed exophytic well-circumscribed, firm, red black mass measuring around 7×5×4 cm sized focally on the left cranial thoracic mammary gland. Upon incision, the mass was filled with black clotted blood. On removal of clots, the tumour tissue appeared as pink and multinodular. Histologically the tumour was highly infiltrative and revealed well differentiated cystic papillary mammary adenocarcinoma with osteogenic metaplasia and minimal stromal invasion. Extensive hemorrhages with moderate inflammatory response were also noticed. Immunohistochemical investigations showed immunopositivity for proliferating cell nuclear antigen (PCNA), ki-67, cyclooxygenase 2 (COX-2), cytokeratin and human epidermal growth factor receptor 2 (HER2).

Calcarea carbonica derivative complex (M8) as adjuvant treatment of inflammatory mammary carcinoma in a dog

Background: Inflammatory mammary carcinoma (IMC) is locally aggressive, fast growing, highly malignant tumor that affects humans and dogs. Affected dogs usually are presented with generalized edema, pain, erythema, and skin ulceration in mammary glands. Surgery is not recommended and an effective treatment has not been established [1]. Calcarea carbonica derivative complex (M8) has demonstrated anticancer properties in a murine model, by improving innate immune response against tumor cells [2,3]. M8 is a complex high diluted medication comprised of a 10%-20% concentration of Calcarea carbonica, Aconitum napellus, Arsenicum album, Asa foetida, Conium maculatum, Ipecacuanha, Phosphorus, Rhus tox, Silicea, Sulphur, and Thuya occidentalis, all in decimal dilutions of Hahnemann in distilled water and submitted to vigorous shaking. &#x0D; &#x0D; Aim: Describe an association of M8 and piroxicam (Non-steroidal anti-inflammatory drug) to treat a dog with IMC.&#x0D; &#x0D; Discussion: A 7 years old, mixed breed intact female dog was presented to the Federal University of Parana - Veterinary Hospital, Curitiba (HV-UFPR) for mammary glands examination. The owners related inflammation of mammary glands with clinical course of approximately 10 days, which was treated for mastitis (cephalexin and metergoline) without clinical improvement. Clinical examination revealed erythema, increased skin warmth, pain on palpation, and plaque involving the 4th and 5th right mammary glands. Abdominal ultrasound and serum biochemistry were unremarkable. Thoracic radiographs showed suspicious images of pulmonary metastasis. Fine needle biopsy was taken for cytologic examination. Cytological interpretation was a malignant epithelial neoplasm, probably a mammary carcinoma. Diagnosis of IMC was based on clinical signs and cytopathology. Dog was treated with oral (0.5 mL) and topical M8 twice a day for 15 days, and pyroxican, 0.3mg/kg, PO, q24h. Clinical improvement was observed 7 days after starting treatment. Until present date (70 treatment days with M8), dog has no clinical signs of IMC, and does not show signs of disease progression.&#x0D; &#x0D; Conclusion: The present report suggests that M8 associated with piroxicam contributes to improvement of IMC dog’s quality of life and survival rate. However, further clinical studies are needed to evaluate response to treatment in patients diagnosed with IMC.

Oral, topical, and inhalation of Calcarea carbonica derivative complex (M8) to treat inflammatory mammary carcinoma in dogs

Background: Inflammatory mammary carcinoma (IMC) is locally aggressive, fast growing, highly malignant tumor that affects humans and dogs. Affected dogs usually are presented with generalized edema, pain, erythema, and skin ulceration in mammary glands. Surgery is not recommended and an effective treatment has not been established [1]. Calcarea carbonica derivative complex (M8) has demonstrated anticancer properties in a murine model, by improving innate immune response against tumor cells [2]. M8 is a complex high diluted medication comprised of Calcarea carbonica 16x, Aconitum napellus 20x, Arsenicum album 18x, Asa foetida 20x, Conium maculatum 17x, Ipecacuanha 13x, Phosphorus 20x, Rhus toxicodendron 17x, Silicea 20x, Sulphur 24x, and Thuya occidentalis 19x, dilution procedures have followed standard methodology described at the Brazilian Homeopathic Pharmacopoeia. &#x0D; Aims: To describe different routes of M8 administration associated with oral pyroxican (non-steroidal anti-inflammatory drug) to treat dogs with IMC.&#x0D; Methodology: Three female dogs with 10 years old median age were presented to the Veterinary Teaching Hospital at Federal University of Parana, Curitiba (HV-UFPR) with cytological and clinical diagnosis of IMC. Patients were treated with oral (0.5 mL,q12h), topical (q12h) and inhalatory (2 mL, q24h, through an ultrasonic inhalation device) M8, and oral pyroxican (0.3mg/kg, q24h).Thoracic radiographs showed pulmonary metastasis in all dogs. &#x0D; Results: 7 days after initiating treatment all patients had clinical improvement. It was observed reduction on mammary glands inflammation and decreased pain sensitivity. One patient had 8 month of complete remission. The other two patients died 1 and 2 month after initial treatment. However none of the patients had pulmonary progressive disease, showed by radiographic examinations. Owners revealed treatment satisfaction in regards to quality of life improvement, easy M8 administration, good M8 palatability for dogs, and inflammation reduction. &#x0D; Conclusion: The present report suggests that M8 influenced positively the anti -inflammatory treatment.&#x0D; Keywords: Calcarea carbonica complex; inflammatory mammary carcinoma; routes of administration&#x0D; References&#x0D; [1] Sorenmo K. Canine mammary gland tumors. Veterinary Clinics of North America: Small Animal Practice. 2003 33(3):573-96.&#x0D; [2] Oliveira CC, Abud APR, Oliveira SM, Guimarães FSF, Andrade LF, Di Bernardi RP, Coletto ELO, Kuczera D, Da Lozzo EJ, Gonçalves JP, Trindade ES, Buchi DF. Developments on drug discovery and on new therapeutics: highly diluted tinctures act as biological response modifiers. BMC Complementary and Alternative Medicine 2011, 11(101): 2-11.

Integrative homeopathic treatment and pharmacopuncture with Viscum album in canine mammary carcinoma: Case report.

Inflammatory mammary carcinoma is a highly aggressive tumor that affects dogs, characterized by progressive disease and a high mortality rate. Affected dogs have diffuse swollen mammary glands with little demarcation between tissues, making the region firm, in the form of plaques, hot and painful on palpation with possible thickening of the skin and sero-bloody secretion. Acupuncture is considered as an adjunctive treatment modality, as it improves the quality of life of cancer patients, in addition to controlling these metabolic changes. This paper reports the case of a female dog treated with pharmacopuncture in association with the Viscum album. The animal arrived with normocardia, eupnea, pale mucous membranes and a lump in the breast region. Preoperative and imaging exams were carried out, followed by a pan-hysterectomy and partial mastectomy procedure, with sample collection for histopathological analysis. A Grade II Mixed Tumor Carcinoma was diagnosed and then the pharmacopuncture treatment with Viscum album was proposed. Sessions were held weekly for 9 months and there was an improvement in the clinical and physical aspect of the animal. The growing development of medicine associated with new treatment techniques promotes better results and favorable quality of life for animals. As a prophylactic measure of the disease, castration remains the best option, especially when used before the first heat.

Canine Inflammatory Mammary Carcinoma as a Promising Model for Cancer Pathology and Anticancer Drug Development: Lessons from a Case Series

Canine Inflammatory Mammary Carcinoma as a Promising Model for Cancer Pathology and Anticancer Drug Development: Lessons from a Case Series

Effects of doxorubicin associated with amniotic membrane stem cells in the treatment of canine inflammatory breast carcinoma (IPC-366) cells

BackgroundTumours in mammary glands represent the most common neoplasia in bitches, as in humans. This high incidence results in part from the stimulation of sex hormones on these glands. Among mammary tumours, inflammatory carcinoma is the most aggressive, presenting a poor prognosis to surgical treatment and chemotherapy. One of the most widely used chemotherapy drugs for breast cancer treatment is doxorubicin (DOXO). Alternative therapies have been introduced in order to assist in these treatments; studies on treatments using stem cells have emerged, since they have anti-inflammatory and immunomodulatory properties. The aim of this study was to evaluate the effects of DOXO and canine amniotic membrane stem cells (AMCs) on the triple-negative canine inflammatory mammary carcinoma cell line IPC-366.MethodsFour experimental groups were analysed: a control group without treatment; Group I with DOXO, Group II with AMC and Group III with an association of DOXO and AMCs. We performed the MTT assay with DOXO in order to select the best concentration for the experiments. The growth curve was performed with all groups (I-III) in order to verify the potential of treatments to reduce the growth of IPC-366. For the cell cycle, all groups (I-III) were tested using propidium iodide. While in the flow cytometry, antibodies to progesterone receptor (PR), estrogen receptor (ER), PCNA, VEGF, IL-10 and TGF-β1 were used. For steroidogenic pathway hormones, an ELISA assay was performed.ResultsThe results showed that cells treated with 10 µg/mL DOXO showed a 71.64% reduction in cellular growth after 72 h of treatment. Reductions in the expression of VEGF and PCNA-3 were observed by flow cytometry in all treatments when compared to the control. The intracellular levels of ERs were also significantly increased in Group III (4.67% vs. 27.1%). Regarding to the levels of steroid hormones, significant increases in the levels of estradiol (E2) and estrone sulphate (S04E1) were observed in Groups I and III. On the other hand, Group II did not show differences in steroid hormone levels in relation to the control. We conclude that the association of DOXO with AMCs (Group III) promoted a reduction in cell growth and in the expression of proteins related to proliferation and angiogenesis in IPC-366 triple-negative cells.ConclusionsThis treatment promoted ER positive expression, suggesting that the accumulated oestrogen conducted these cells to a synergistic state, rendering these tumour cells responsive to ERs and susceptible to new hormonal cancer therapies.

Exploration of the developmental process of vasculogenic mimicry in canine inflammatory mammary carcinoma

Canine inflammatory mammary carcinoma (CIMC) similar to human inflammatory breast cancer is a very aggressive, metastatic type of cancer. Previous studies have introduced a new type of tumor angiogenesis called vasculogenic mimicry that may play an important role in the progression of inflammatory mammary cancer. The purpose of this study is to investigate the development process of vessels by neoplastic cells in CIMC. Patient dog, 14-year old Shit-Tzu female, had a hard and somewhat movable dark-reddish mammary tumor, sized 6.2 cm in diameter. Bloody dark turbid exudate was released from the tumor. In addition to histological examination, immunohistochemistry for pancytokeratin, VCAM-1, MECA-32, TWIST-1, and Ki-67 was respectively performed using the ABC method. Histologically, the inflammatory mammary carcinoma was characterized by tubular solid tumor emboli within the lymphatic vessels surrounded by desmoplastic fibrous connective tissue. Some of the neoplastic cells were transforming into elongate or spindle shapes and forming small vessel-like structures in the solid tumor mass. The neoplastic cells were immunoreactive for VCAM-1 and MECA-32, but showed low immunoreactivity for Ki-67. Immunoreactive neoplastic cells for VCAM-1 and MECA-32 suggested the possibility that the neoplastic cells transform into endothelial cells of vessels by epithelial-mesenchymal transition, further supported by serial morphological changes identified by histological investigation and immunohistochemistry for TWIST-1. The high capacity of the neoplastic cells forming the vasculatures in CIMC explains the high ratio of metastasis to other regions, even though Ki-67 index was not so high.

Inflammatory mammary carcinoma with histological presentation of a well-differentiated mixed malignant tumor - Case report

Inflammatory mammary carcinoma with histological presentation of a well-differentiated mixed malignant tumor - Case report

The impact of toceranib, piroxicam and thalidomide with or without hypofractionated radiation therapy on clinical outcome in dogs with inflammatory mammary carcinoma.

In dogs, inflammatory mammary carcinoma is a clinicopathological entity characterized by rapid progression and aggressive behavior from onset of disease. Reported median survival time is short, with no effective treatment options. The aims of this prospective, noncontrolled clinical trial were to investigate outcome variables and safety profile of toceranib, thalidomide and piroxicam with or without hypofractionated radiation therapy in dogs with measurable histologically confirmed inflammatory mammary carcinoma that underwent a complete staging. Eighteen dogs were enrolled: 14 received medical treatment, and 4 were treated with hypofractionated radiation therapy and medical therapy. Overall, median time to progression was 34 days and median survival time was 109 days. In dogs treated with medical therapy, overall response rate was 21%, and clinical benefit rate (CBR) was 64%; median time to progression was 28 days and median survival time was 59 days. In dogs receiving medical therapy and undergoing radiation therapy, overall response rate and clinical benefit rate were 100%, with significantly longer time to progression (156 days) and survival time (180 days). Overall, treatment was well tolerated, with mild gastrointestinal and dermatological adverse events. Although the optimal treatment to this disease remains uncertain, the current approach consisting of systemic anti-angiogenic drugs with or without hypofractionated radiation therapy, provided clinical benefit in a significant proportion of dogs and should, therefore, be further explored.

CARCINOMA INFLAMATÓRIO DE MAMA – UMA ABORDAGEM COMPARADA

O Carcinoma Inflamatório de Mama (CIM) é um neoplasma maligno de rápida evolução que apresenta baixa ocorrência tanto em cadelas quanto em mulheres. É pouco relatado pelos médicos veterinários no Brasil, fato que pode ser relacionado à falta de conhecimento da doença associado à necessidade da relação dos achados clínicos com exame histopatológico para o diagnóstico definitivo. Esse neoplasma também acomete a glândula mamária de mulheres, nas quais demonstra características clássicas de inflamação como dor, turgor de pele e aumento de temperatura local. Para diagnóstico definitivo é considerado a presença de êmbolos de células tumorais em canais linfáticos da derme associados aos sinais clínicos de inflamação. Devido ao grau de infiltração local, os sinais de inflamação e a presença de êmbolos em linfáticos, o paciente humano e veterinário apresentam prognóstico desfavorável. O CIM é pouco responsivo à quimioterapia e devido às características de inflamação, não apresenta indicação cirúrgica na maioria dos casos. Devido à agressividade do CIM em mulheres e nas cadelas, do prognóstico desfavorável e das restritas opções terapêuticas essa revisão objetiva descrever os avanços das opções terapêuticas além do tratamento paliativo na literatura atual além de apresentar uma abordagem comparada, considerando a cadela um modelo de estudo para a doença na mulher.

Inflammatory Mammary Carcinoma with Disseminated Tumour Embolism in a Dog

Inflammatory Mammary Carcinoma with Disseminated Tumour Embolism in a Dog

Steroid hormone secretion in inflammatory breast cancer cell lines.

Inflammatory breast carcinoma (IBC) is a special type of breast cancer with a poor survival rate. Though several IBC cell lines have been established, recently a first IMC cell line was established. The aims of this study were: (1) to validate a highly sensitive, reliable, accurate and direct amplified enzyme immunoassay (EIA) to measure several cell-secreted steroid hormones: progesterone (P4), androstenedione (A4), testosterone (T), 17β-estradiol (E2) and estrone sulfate (SO4E1) in the culture medium. (2) To assess whether hormone production profile by IPC-366 cells validates the IMC model for human IBC. We validated a non-competitive amplified EIA for inflammatory breast cancer cell lines based on the results of accuracy, precision, sensitivity and parallelism. The low detection limits of the technique were: P4=13.2 pg/well, A4=2.3 pg/well, T=11.4 pg/well, E2=1.9 pg/well and SO4E1=4.5 pg/well. Intra- and inter-assay coefficient of variation percentages were <10%. The mean recovery rate of hormone added to the culture medium was >90%. In all hormones studied SUM149 have higher levels (1.4 times, but not significant) than IPC-366, and the correlation index between SUM149 and IPC-366 concentrations were >97%. We can coclude that cells of both cell lines, IPC-366 and SUM149, are capable to produce steroid hormone in culture media. The presented EIA methodology is very valuable for the detection of steroid production in culture media and could be used in hormone regulation studies and therapeutic agents in cell lines of inflammatory and non-inflammatory mammary carcinoma or other cancer cell lines in preclinical studies.

Abstract P5-07-04: Characterization of a new canine inflammatory mammary cancer (IMC) cell line (IPC-366)

Abstract Spontaneous canine inflammatory mammary cancer (IMC) shares epidemiologic, histopathological and clinical characteristics with the disease in humans and has been proposed as a natural model for human inflammatory breast cancer (IBC). Few cell lines are available to study IBC, such us SUM 149, SUM 190 and MDA-IBC3. The aim of this study was to characterize a new cell line from IMC (IPC-366) for the comparative study of both IMC and IBC. Tumors cells from a female dog with clinical IMC were collected. The pathological diagnosis of IMC was confirmed at the Veterinary Pathology Service of UCM- Veterinary Clinical Hospital. The cells were grown under adherent conditions in DMEM/F12 with 5% fetal bovine serum and 1% antibiotics (streptomycin and penicillin). The growth and mammospheres production capability, and cytological, ultrastructural and immunohistochemical (IHC) characteristics of IPC-366 were evaluated. Tumorigenicity and metastatic potential of IPC-366 were also assessed by inoculating the cells on the mammary fat pad of 18 female Balb/SCID mice and the development of tumor was monitored by imaging and luciferase assay. Microscopic examination of tumor revealed an epithelial morphology with marked anysocytosis. Doubling time of the tumor cells was approximately 24 h. Under non-adherent conditions, IPC-366 cells formed mammospheres in approximately 3 days. Cytological and histological examination of smears and ultrathin sections by electron microscopy revealed that IPC-366 is formed by highly malignant large round or polygonal cells characterized by marked atypia and prominent nucleoli and frequent multinucleated cells. Some cells had cytoplasmic empty spaces covered by cytoplasmic membrane resembling capillary endothelial cells, a phenomenon described as vasculogenic mimicry. IHC characterization of IPC-366 was basal-like: epithelial cells (AE1/AE3+, CK14+, vimentin+, actin-, p63-, ER-, PR-, HER-2 – (DAKO, HER2 P4 ), overexpressed COX-2 and high Ki-67 proliferation index (87.15 %). Imaging and luciferase assay revealed that at 3 weeks after inoculating the IPC-366 cells, a tumor mass was found in 50 % of mice. At 8 weeks after inoculation metastases in lung, liver and lymph nodes were found. Xenograph tumors maintained the original IHC characteristics of the female dog tumor. In summary, the cell line IPC-366 is a fast growing malignant triple negative cell line model of inflammatory mammary carcinoma that can be used for the comparative study of both IMC and IBC. Citation Format: Sara Caceres, Laura Peña, Lara C Alvarez de la Cerda, Maria J Illera, Richard Larson, Hui Gao, Bisrat G Debeb, Wendy A Woodward, James M Reuben, Juan C Illera. Characterization of a new canine inflammatory mammary cancer (IMC) cell line (IPC-366) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-07-04.

Establishment and characterization of a new cell line of canine inflammatory mammary cancer: IPC-366.

Canine inflammatory mammary cancer (IMC) shares epidemiologic, histopathological and clinical characteristics with the disease in humans and has been proposed as a natural model for human inflammatory breast cancer (IBC). The aim of this study was to characterize a new cell line from IMC (IPC-366) for the comparative study of both IMC and IBC. Tumors cells from a female dog with clinical IMC were collected. The cells were grown under adherent conditions. The growth, cytological, ultrastructural and immunohistochemical (IHC) characteristics of IPC-366 were evaluated. Ten female Balb/SCID mice were inoculated with IPC-366 cells to assess their tumorigenicity and metastatic potential. Chromosome aberration test and Karyotype revealed the presence of structural aberration, numerical and neutral rearrangements, demonstrating a chromosomal instability. Microscopic examination of tumor revealed an epithelial morphology with marked anysocytosis. Cytological and histological examination of smears and ultrathin sections by electron microscopy revealed that IPC-366 is formed by highly malignant large round or polygonal cells characterized by marked atypia and prominent nucleoli and frequent multinucleated cells. Some cells had cytoplasmic empty spaces covered by cytoplasmic membrane resembling capillary endothelial cells, a phenomenon that has been related to s vasculogenic mimicry. IHC characterization of IPC-366 was basal-like: epithelial cells (AE1/AE3+, CK14+, vimentin+, actin-, p63-, ER-, PR-, HER-2, E-cadherin, overexpressed COX-2 and high Ki-67 proliferation index (87.15 %). At 2 weeks after inoculating the IPC-366 cells, a tumor mass was found in 100 % of mice. At 4 weeks metastases in lung and lymph nodes were found. Xenograph tumors maintained the original IHC characteristics of the female dog tumor. In summary, the cell line IPC-366 is a fast growing malignant triple negative cell line model of inflammatory mammary carcinoma that can be used for the comparative study of both IMC and IBC.

Clinical and prognostic implications of serum and tissue prolactin levels in canine mammary tumours

The biological implications of serum and tissue prolactin levels in canine mammary tumours (CMT) have been previously described although the influence of this hormone on inflammatory mammary carcinomas as well...