Centro de Investigaciones Inmunológicas Básicas y Aplicadas (CINIBA)

Integrative functional genomics analysis of Kaposi sarcoma cohorts

2026-04-27T20:25:44Z

Articulo Scientific Reports; vol. 15 no. 1 Kaposi sarcoma (KS) is an AIDS-defining cancer and a significant global health challenge caused by KS-associated herpesvirus (KSHV). NGS-based approaches have profiled KS lesions in a minimal number of studies compared with other neoplastic diseases. Here we present a compiled and harmonized dataset of 131 KS and non-tumor cutaneous samples in the context of their predicted pathway activities, immune infiltrate, KSHV and HIV gene expression profiles, and their associated clinical data representing patient populations from Argentina, United States (USA), and Sub-Saharan Africa cohorts. RNA-seq data from 9 Argentinian KS lesions were generated and integrated with previously published datasets derived from the USA and sub-Saharan African cohorts from Tanzania, Zambia, and Uganda. An unsupervised analysis of 131 KS-related samples allowed us to identify four KS clusters based on their host and KSHV gene expression profiles, immune infiltrate, and the activity of specific signaling pathways. The compiled RNA-seq profile is shared with the research community through the UCSC Xena browser for further visualization, download, and analysis ( https://kaposi.xenahubs.net/ ). These resources will allow biologists without bioinformatics knowledge to explore and correlate the host and viral transcriptome in a curated dataset of different KS RNA-seq-based cohorts, which can lead to novel biological insights and biomarker discovery.

MUC1 and carbohydrate associated antigens in head and neck squamous cell carcinoma: our experience

2025-12-18T04:26:50Z

Articulo Journal of Immunological Sciences; vol. 2, no. 3 Head and neck cancer constitutes the sixth cause of cancer worldwide with an age-standardized rate of 9.1 cases per 100,000 inhabitants, not including thyroid tumors. Most stage I/II patients have a very good prognosis while those with higher stages of the disease show a poor overall survival being the presence of lymph node metastases the main factor. Development of tumor markers either prognostic as well as to detect early recurrences or therapy-predictive would have critical importance. In the last years, several publications related to immunotherap, genomics and viral carcinogenesis have explored new biological targets and markers for this disease.

Detección de integrinas en vesículas extracelulares grandes de pacientes con cáncer de mama

2025-08-26T04:16:04Z

Objeto de conferencia !! Workshop Anual del Grupo Argentino de Vesículas Extracelulares (GAVE) (Buenos Aires, 12 y 13 de septiembre de 2024) Los tumores liberan en la circulación periférica vesículas de distintos orígenes. Aquellas procedentes de la membrana plasmática son potenciales portadoras de moléculas de adhesión celular relacionadas con los procesos de diseminación tumoral. Con el fin de analizar la expresión de integrinas en vesículas extracelulares de pacientes con cáncer de mama, a partir de plasma almacenado a -80°C se aislaron mediante centrifugación diferencial fracciones de vesículas membranosas a 400 xg, 1500 xg, 10.000 xg y, luego de resuspender el pellet con PBS, nuevamente a 10.000 xg, sucesivamente. Cada centrifugación duró 30 minutos, a 4°C. Finalmente, el último pellet fue resuspendido con PBS, fraccionado y almacenado a -80°C. Se evaluó la concentración de proteínas de las fracciones. El tamaño y forma de las vesículas fue determinado mediante dispersión dinámica de la luz (DLS) y microscopía electrónica (EM). Las fracciones fueron analizadas mediante inmunoblot para la detección de CD9, CD63, integrina α6 e integrina β4. Resultados: De 43 muestras 41 mostraron material membranoso y concentraciones de proteínas suficientes para el estudio. El análisis mediante DLS y EM mostró vesículas membranosas de más de 200 nm, con agregados de vesículas y un promedio superior a 400 nm mediante DLS. Los inmunoblot mostraron reacción positiva para CD9 en 5/41 (12,2), para CD63 en 10/41 (24,4), para integrina α6 en 27/41 (65,9) y para integrina β4 en 5/41 (12,2). Conclusión: Algunas de las fracciones de plasma de pacientes con cáncer de mama contienen vesículas extracelulares grandes, portadoras de integrinas α6 y β4.

COVID-19: A study about the Impact of Coronavirus on Physicians of La Plata, Argentina

2023-11-02T20:07:32Z

Articulo Anesthesia and Critical Care; vol. 5, no. 1 Background: In Argentina, the burden of COVID-19 on health systems and physicians was substantial with difficulties on daily triage decisions which have to be made in the context of grave shortages of basic equipment and consumables. Purpose: this study was performed to understand what physicians were experiencing during the COVID-19 pandemic in La Plata (capital city of Buenos Aires province, Argentina). Methods: A cross-sectional study was performed; a questionnaire was sent by e-mail to physicians who work in this city during November 2020. The questionnaire was made based on Medscape US and International Physicians' COVID-19 Experience Report: Risk, Burnout, Loneliness. Statistical analysis: test for normality was performed employing the Kolmogorov-Smirnov test while Chi-square test of independence to examine the relationship between sex and workplace with nominal variables. For categorical variables, Kendall’s tau correlation was performed to test for independence. ANOVA was developed to examine differences between physician’s age. Statistical significance was set to p <0.05 in all cases. All statistical analysis was done employing SPSS Statistics, Version 24 (IBM, USA). Results: 203 physicians answered the questionnaire; the majority of physicians (96%) considered stressful their experience during pandemic and reported distress episodes being for more than 60% the most stressful of their practices, 30% presented depression and were medically treated, while 32.7% felt loneliness with 4 physicians with suicidal thoughts. Conclusion: The results highlight the need to protect the psychological well-being of the healthcare community, and to invest resources to significantly promote the mental health of professionals.

The Relevance of Cultural, Fatalistic and Psychosocial Factors in Breast Cancer Screening Behavior in Middle Age and Older Women

2023-11-01T20:07:23Z

Articulo Fortune Journal of Health Science; vol. 6, no. 1 The aim of this study was to analyze cultural and social factors in advantaged and disadvantaged women in relation to mammographic screening. A cross-sectional study was performed; 850 women aged 45-79 years were interviewed; based on socioeconomic aspects, women were grouped in low economic power (Low group, LG) (379 women) and middle economic power (MG) (471). A questionnaire previously validated was employed and information about cultural, fatalistic, and psychosocial factors as well as breast cancer and mammographic screening was assessed. An extensive statistical analysis was performed including three regression models and a principal component analysis. 98% MG and 49.7% LG had a high level of education. Women who stated having a high level of education, regularly visit a doctor and being communicatively open showed the most positive mammographic screening behaviors. In general, analysis of fatalistic affirmatives in relation to mammogram variables did not show a significant difference in relation to total MG and LG while psychosocial variables showed a very low significant relationship with mammographic screening. Regression analysis showed similar results. This study highlights that communication as well as family and social support constitute important factors which impact on mammographic screening, while fatalism, although present, should not constitute a crucial aspect.

Breast cancer cutaneous metastases are associated to uMUC1 and sialyl Lewis x and to highly malignant primary tumors

2023-11-01T20:07:25Z

Articulo Pathology - Research and Practice; vol. 216, no. 4 Breast cancer spreading to different organs have been related to different molecules and mechanisms, but cutaneous metastasis remains unexplored. Increasing evidence showed that MUC1 and some of its carbohydrate associated antigens may be implicated in breast cancer metastasis. In this study we analyzed these tumor markers in order to identify breast cancer cutaneous metastatic profiles. A cohort of 26 primary tumors from breast cancer patients with cutaneous metastases were included; also, cutaneous and lymphatic node metastatic samples and primary tumors from breast cancer patients without metastases were analysed. Immunohistochemical (IHC) studies demonstrated that both underglycosylated MUC1 (uMUC1) and sialyl Lewis x (sLex) to be positively associated with cutaneous metastatic primary tumors (p < 0.05). Notably, a high percentage of tumors with cutaneous metastases were characterized as triple negative and Her2+ tumors (37.5 % and 29 %, respectively). Some discordant results were found between primary tumors and their matched cutaneous metastases. To determine if MUC1 variants may be carriers of carbohydrate antigens, subcellular fractions from a cutaneous metastatic lesion were obtained, immunoprecipitated and analyzed by Western blot. We found that the isolated uMUC1 with a molecular weight of>200 kDa was also the site for binding of antisLex MAb; in coincidence, a high correlation of positive IHC expression of both markers was observed. Our findings confirm that breast cancer cutaneous metastases were associated to highly malignant primary tumors and sustain the hypothesis that u-MUC1 and sLe x may drive breast cancer cutaneous metastases.

Factors associated with breast cancer in an Argentine city

2023-10-31T20:08:17Z

Articulo The Breast Journal; vol. 24, no. 6 In Argentina, breast cancer is the most commonly diagnosed cancer and the first leading cause of cancer deaths; this information is mainly based on estimations since only recently, Argentina has organized a National Registry of Tumors. Argentine studies addressing socioeconomic factors and their possible effect on breast cancer prevalence are scarce, and there is not any systematic action to prevent and control breast cancer as well. The aim of this study was to explore the relationship among socioeconomic factors, breast cancer risk factors, women's adherence to mammography screening, and breast cancer prevalence in La Plata, the capital city of Buenos Aires Province (Argentina), an administrative and University city. We performed a cross‐sectional study of women with low socioeconomic power (low group, LG) and a middle group (MG) from October 2012 to December 2012; 739 women between 45 and 79 years old were personally interviewed, being 360 (MG) and 379 (LG). A structured questionnaire previously validated was employed. Variables included were as follows: socioeconomic group, breast cancer risk and socioeconomic factors, mammographic screening parameters, ever diagnosed breast cancer, Physician Enrollment, and Health System which consists of three sectors: Public (free), Private, and Social/Union Security.

Hemoxygenase-1 Promotes Head and Neck Cancer Cell Viability

2023-08-02T04:06:43Z

Articulo Antioxidants; vol. 11, no. 10 Head and neck squamous cell carcinoma (HNSCC) is a remarkably heterogeneous disease with around 50% mortality, a fact that has prompted researchers to try new approaches to improve patient survival. Hemoxygenase-1 (HO-1) is the rate-limiting step for heme degradation into carbon monoxide, free iron and biliverdin. We have previously reported that HO-1 protein is upregulated in human HNSCC samples and that it is localized in the cytoplasmic and nuclear compartments; additionally, we have demonstrated that HO-1 nuclear localization is associated with malignant progression. In this work, by using pharmacological and genetic experimental approaches, we begin to elucidate the mechanisms through which HO-1 plays a role in HNSCC. We found that high HO-1 mRNA was associated with decreased patient survival in early stages of HNSCC. In vitro experiments have shown that full-length HO-1 localizes in the cytoplasm, and that, depending on its enzymatic activity, it increases cell viability and promotes cell cycle progression. Instead, HO-1 does not alter migration capacity. Furthermore, we show that C-terminal truncated HO-1 localizes into the nucleus, increases cell viability and promotes cell cycle progression. In conclusion, we herein demonstrate that HO-1 displays protumor activities in HNSCC that depend, at least in part, on the nuclear localization of HO-1.

Galectin-1 fosters an immunosuppressive microenvironment in colorectal cancer by reprogramming CD8⁺ regulatory T cells

2022-11-29T04:05:53Z

Articulo Proceedings of the National Academy of Sciences; vol. 118, no. 21 Colorectal cancer (CRC) represents the third most common malignancy and the second leading cause of cancer-related deaths worldwide. Although immunotherapy has taken center stage in mainstream oncology, it has shown limited clinical efficacy in CRC, generating an urgent need for discovery of new biomarkers and potential therapeutic targets. Galectin-1 (Gal-1), an endogenous glycan-binding protein, induces tolerogenic programs and contributes to tumor cell evasion of immune responses. Here, we investigated the relevance of Gal-1 in CRC and explored its modulatory activity within the CD8⁺ regulatory T cell (Treg) compartment. Mice lacking Gal-1 (Lgals1 -/- ) developed a lower number of tumors and showed a decreased frequency of a particular population of CD8⁺CD122⁺PD-1⁺ Tregs in the azoxymethane-dextran sodium sulfate model of colitis-associated CRC. Moreover, silencing of tumor-derived Gal-1 in the syngeneic CT26 CRC model resulted in reduced number and attenuated immunosuppressive capacity of CD8⁺CD122⁺PD-1⁺ Tregs, leading to slower tumor growth. Moreover, stromal Gal-1 also influenced the fitness of CD8⁺ Tregs, highlighting the contribution of both tumor and stromal-derived Gal-1 to this immunoregulatory effect. Finally, bioinformatic analysis of a colorectal adenocarcinoma from The Cancer Genome Atlas dataset revealed a particular signature characterized by high CD8⁺ Treg score and elevated Gal-1 expression, which delineates poor prognosis in human CRC. Our findings identify CD8⁺CD122⁺PD-1⁺ Tregs as a target of the immunoregulatory activity of Gal-1, suggesting a potential immunotherapeutic strategy for the treatment of CRC.

Prevención del cáncer de mama (PRECANMA)

2023-09-21T18:57:25Z

Objeto de conferencia XI Congreso Iberoamericano de Extensión Universitaria (Santa Fe, 22 al 25 de noviembre de 2011) En nuestro país, el cáncer de mama es la enfermedad neoplásica maligna más frecuente en el sexo femenino y constituye un serio problema de salud ya que 1 de cada 8 mujeres padecen o tendrán la enfermedad en su vida. El presente proyecto de extensión tuvo por objetivo informar a una parte de la población femenina que asiste a las Unidades Sanitarias del Gran La Plata acerca de las medidas de prevención del cáncer de mama. Se realizó con docentes de la Facultad de Ciencias Médicas y con la participación de estudiantes avanzados de Medicina para las charlas didácticas y de estudiantes de Antropología para realizar las encuestas a las mujeres a las cuales iba dirigida la instrucción. Con una antelación de 15 a 20 días previos a las charlas informativas, los estudiantes fueron a los barrios repartiendo volantes por las casas tratando de motivar a las mujeres para lograr su asistencia a las charlas dando la fecha de realización de la charla. Posteriormente, el día fijado, se realizaron las encuestas y posteriormente las charlas informativas con la participación de los docentes y estudiantes de Medicina. Los folletos fueron realizados por alumnas de la Carrera de Diseño de la UNLP; asimismo, estas alumnas realizaron el diseño de paneles que fueron empleados para las charlas informativas en las Unidades Sanitarias. Se pudo comprobar una activa participación de los estudiantes de todas las carreras involucradas así como una gran participación de las mujeres invitadas a las charlas que asistieron contestando las preguntas de la encuesta y con gran interés en la información brindada.

Lewis x Antigen is Associated to Head and Neck Squamous Cell Carcinoma Survival

2022-10-25T20:06:43Z

Articulo Pathology and Oncology Research; vol. 24, no. 3 Head and neck squamous cell carcinoma (HNSCC) is an aggressive disease with poor prognosis without appropriate prognostic markers. Previous research shows that Lewis antigens have been involved in carcinoma dissemination and patients´ survival. Fucosyl and sialyltransferases are the enzymes implicated in the Lewis antigens synthesis. The purpose of this study was to evaluate the prognostic utility of Lewis antigens in HNSCC. We conducted a prospective research including histological samples from 79 patients with primary HNSCC. Lewis x and sialyl Lewis x expression were detected by immunohistochemistry; patient's data, progression free, and overall survival were documented. A statistical correlation study of antigenic expression and patients´ histopathological variables was performed. Cox regression models with internal validation procedures were employed to analyze survival data. By immunohistochemistry, Lewis x was detected in 34/79 (43%) tumor samples, while sialyl Lewis x only in 11/79 (14%). Lewis x expression showed a positive correlation with tumor differentiation and a better overall survival for Lewis x + patients was detected. Moreover, multivariate Cox's regression analysis showed that Lewis x is an independent predictor of better overall survival. The in silico analysis supported the presence of deregulated fucosyl (FUT4) and sialyltransferase (ST3GAL4) in the Lewis synthetic pathway related to patient survival. These results suggest that Lewis x expression is associated with a better outcome in patients with HNSCC.

Identification of an AP1-ZFP36 Regulatory Network Associated with Breast Cancer Prognosis

2022-10-04T04:04:02Z

Articulo Journal of Mammary Gland Biology and Neoplasia; vol. 25, no. 2 It has been established that ZFP36 (also known as Tristetraprolin or TTP) promotes mRNA degradation of proteins involved in inflammation, proliferation and tumor invasiveness. In mammary epithelial cells ZFP36 expression is induced by STAT5 activation during lactogenesis, while in breast cancer ZFP36 expression is associated with lower grade and better prognosis. Here, we show that the AP-1 transcription factor components, i.e. JUN, JUNB, FOS, FOSB, in addition to DUSP1, EGR1, NR4A1, IER2 and BTG2, behave as a conserved co-regulated group of genes whose expression is associated to ZFP36 in cancer cells. In fact, a significant down-modulation of this gene network is observed in breast, liver, lung, kidney, and thyroid carcinomas compared to their normal counterparts. In breast cancer, the normal-like and Luminal A, show the highest expression of the ZFP36 gene network among the other intrinsic subtypes and patients with low expression of these genes display poor prognosis. It is also proposed that AP-1 regulates ZFP36 expression through responsive elements detected in the promoter region of this gene. Culture assays show that AP-1 activity induces ZFP36 expression in mammary cells in response to prolactin (PRL) treatment thorough ERK1/2 activation. These results suggest that JUN, JUNB, FOS and FOSB are not only co-expressed, but would also play a relevant role in regulating ZFP36 expression in mammary epithelial cells.

Mammary differentiation induces expression of Tristetraprolin, a tumor suppressor AU-rich mRNA-binding protein

2022-10-01T04:05:21Z

Articulo Breast Cancer Research and Treatment; vol. 135, no. 3 Tristetraprolin (TTP) is a RNA-binding protein that inhibits the expression of pro-inflammatory cytokines and invasiveness-associated genes. TTP levels are decreased in many different cancer types and it has been proposed that this protein could be used as a prognostic factor in breast cancer. Here, using publicly available DNA microarray datasets, “serial analysis of gene expression” libraries and qRT-PCR analysis, we determined that TTP mRNA is present in normal breast cells and its levels are significantly decreased in all breast cancer subtypes. In addition, by immunostaining, we found that TTP expression is higher in normal breast tissue and benign lesions than in infiltrating carcinomas. Among these, lower grade tumors showed increased TTP expression compared to higher grade cancers. Therefore, these data indicate that TTP protein levels would provide a better negative correlation with breast cancer invasiveness than TTP transcript levels. In mice, we found that TTP mRNA and protein expression is also diminished in mammary tumors. Interestingly, a strong positive association of TTP expression and mammary differentiation was identified in normal and tumor cells. In fact, TTP expression is highly increased during lactation, showing good correlation with various mammary differentiation factors. TTP expression was also induced in mammary HC11 cells treated with lactogenic hormones, mainly by prolactin, through Stat5A activation. The effect of this hormone was highly dependent on mammary differentiation status, as prolactin was unable to elicit a similar response in proliferating or neoplastic mammary cells. In summary, these studies show that TTP expression is strongly linked to the mammary differentiation program in human and mice, suggesting that this protein might play specific and relevant roles in the normal physiology of the gland.

Counterbalance of Foxp3 and IDO expression at different tumor stages in aggressive breast cancer subtypes

2022-09-27T04:04:43Z

Preprint Foxp3 and IDO1 are known immunomodulatory molecules involved in tumor escape and could be related to tumor infiltrating lymphocytes (TILs) in the tumor microenvironment. In this study, tumoral Foxp3 and IDO1 expression in breast cancer were evaluated in relation to lymphocyte biomarkers such as CD8 and CD45R0, regulatory T cells, as well as intratumoral and stromal TILs (iTILs and sTILs, respectively). Clinical and histopathological features were also included in the analysis. Foxp3 and IDO1 were found in tumor cells showing mainly cytoplasmic patterns in 60% and 62% tumor samples, respectively. TILs were found in 76% of samples; iTILs were detected in 92% of those samples and sTILs in 55%. Foxp3+ TILs were detected only in 12% of TILs+ samples associated with tumoral Foxp3 expression. Tumoral Foxp3 was mainly expressed at lower tumor stages while IDO1 expression was associated with advanced tumor stages; both correlated with CD8+ TILs which were observed in 77% of TILs+ samples. CD45R0+ were observed in 81% of TILs+ samples and correlated with higher tumor stages and poorly differentiated tumors. In ER negative tumors, an inverse correlation between Foxp3 and IDO1 tumoral expression was found in relation to tumor stage. TNBC subtype showed a positive correlation with the presence of iTILs. In silico analysis showed that Foxp3 and coexpressed genes in breast cancer were associated with immune response genes. Foxp3 was found predominantly in Basal and Her2-enriched subtypes in relation to Luminal A subtype, by RNA seq and RNA microarray database analysis. In conclusion, the expression of Foxp3 and IDO1 in tumors at different stages suggests a potential compensatory mechanism to evade the strong CTL response observed. This is relevant since the cumulative data indicates that Foxp3 as well as IDO1 could be potential targets of immunotherapy in patients with tumors at different stages and for the most aggressive breast cancer subtypes such as TNBC and Her2-enriched.

IgM anti-phenolic glycolipid I and IgG anti-10-kDa heat shock protein antibodies in sera and immune complexes isolated from leprosy patients with or without erythema nodosum leprosum and contacts

2022-09-02T04:04:39Z

Articulo FEMS Immunology and Medical Microbiology; vol. 19, no. 1 The aim of the present work was to evaluate the levels of anti-PGL-I and anti-10-kDa heat shock protein antibodies in serum and immune complexes isolated from leprosy patients, convivients and controls. Leprosy patients with erythema nodosum leprosum or without it were included and a comparative study was done to investigate intergroup differences. Immune complexes were precipitated from serum by polyethylene glycol 3.5%; antibody levels were measured in sera and in dissociated immune complexes by ELISA. Serum antibody levels were then correlated with immune complex-associated antibody levels. The results showed that the erythema nodosum leprosum group differed from controls, contacts and non-erythema patients in their immune complex levels. IgM anti-PGL-I and IgG anti-10-kDa heat shock protein antibodies were constituents of the immune complexes in patients with erythema nodosum leprosum, who exhibited a significant difference in their immune complex composition compared with controls, contacts and non-erythema patients; while free antibody levels (anti-PGL-I and anti-10-kDa) did not differentiate between erythema and non-erythema patients, the measurement of immune complex-associated antibodies demonstrated a significant difference between the two clinical conditions. Furthermore, the measurement of immune complex-associated anti-PGL-I IgM made it possible to differentiate between contacts and controls. The significance of these results is discussed.

Rhomboid family gene expression profiling in breast normal tissue and tumor samples

2022-08-26T04:04:12Z

Articulo Tumor Biology; vol. 35, no. 2 Rhomboid is an evolutionary conserved and functionally diversified group of proteins composed of proteolytically active and inactive members that are involved in the modulation of multiple biological processes such as epidermal growth factor receptor signaling pathway, endoplasmic reticulum-associated degradation, cell death, and proliferation. Recently, several human rhomboid genes have been associated with the development of chronic myeloid leukemia and pituitary, colorectal, ovarian, and breast cancers. In this study, we evaluated the mRNA and protein expression profiles of rhomboid genes in cancer cell lines and breast tissue/tumor samples. In silico analysis of publicly available gene expression datasets showed that different rhomboid genes are specifically expressed according to the breast cancer intrinsic subtypes. Quantitative reverse transcription–polymerase chain reaction (RT-PCR) analysis showed a significant RHBDD2 mRNA overexpression in advanced breast cancer compared with normal tissue samples (p = 0.012). In addition, we found that RHBDL2 and PARL mRNA expression was associated with a low/intermediate histologic tumor grade (p = 0.024 and p = 0.015, respectively). Immunohistochemistry analysis showed a significant increase of RHBDD2 protein expression in association with breast cancer samples negative for progesterone receptor (p = 0.015). Moreover, protein expression analysis corroborated the quantitative RT-PCR results, indicating that breast primary tumors belonging to patients with a more disseminated disease expressed significantly increased levels of RHBDD2 protein compared with less disseminated tumors (p = 0.01).

RHBDD2: a 5-fluorouracil responsive gene overexpressed in the advanced stages of colorectal cancer

2022-03-30T04:06:15Z

Articulo Tumor Biology; vol. 33, no. 6 In previous studies, we identified rhomboid domain containing 2 (RHBDD2) gene to be markedly overexpressed in breast cancer patients that developed recurrence of the disease. In this study, we evaluated for the first time RHBDD2 gene expression in colorectal cancer (CRC). Five public available DNA microarray studies were compiled in a homogeneous dataset of 906 colorectal samples. The statistical analysis of these data showed a significant increase of RHBDD2 expression in the advanced stages of CRC (p < 0.01). We validated these findings by immunohistochemistry on 130 colorectal tissue samples; RHBDD2 protein overexpression was also observed in the advanced stages of the disease (p < 0.001). In addition, we investigated RHBDD2 expression in response to the chemotherapy agent 5-fluorouracile (5FU). We detected a significant increase of RHBDD2 mRNA and protein after 5FU treatment (20–40 μM; p < 0.001). Overall, these results showed that RHBDD2 overexpression might play a role in colorectal cancer progression.

Alternative splicing variant of RHBDD2 is associated with cell stress response and breast cancer progression

2022-02-22T20:06:10Z

Articulo Oncology Reports; vol. 40, no. 2 RHBDD2 is an intramembrane pseudoprotease member of the Rhomboid superfamily. Our previous studies in breast and colorectal cancer indicate an association between RHBDD2 overexpression and advanced tumor stages. Two alternative transcriptional variants have been described for RHBDD2, which would be encoding for different RHBDD2 protein isoforms. The expression of these RHBDD2 variants/isoforms and its association with breast cancer was the focus of this study. First, expression of RHBDD2 splicing variants was evaluated in normal and breast tumor samples. RHBDD2 variant 2 overexpression was detected in tumors in respect to normal breast tissues at the mRNA and protein levels (P<0.05). Moreover, RHBDD2 variant 2 expression was associated with poor prognostic factors such as basal‑like intrinsic subtype (P<0.05), high proliferation (P<0.01) and long‑term risk‑of‑recurrence (P<0.01) scores. Second, the expression of both variants was evaluated under nutritional‑deprived conditions in breast cancer cell lines. Results demonstrated that RHBDD2 splicing was switched from mRNA variant 1 to variant 2 in association with a significant increment of protein isoform B in response to glucose starvation treatment. Therefore, we propose that the switch from the RHBDD2 variant 1, expressed in normal epithelial cells, to variant 2 occurs as an adaptive phenotype to bypass the stressful tumor microenvironment and promote tumor progression. Finally, the RHBDD2 subcellular localization was corroborated at the Golgi apparatus and their associated v‑SNARE transport vesicles, suggesting a putative new role for RHBDD2 in the protein trafficking of human breast cancer cells.

Breast Cancer Risk and Prognostic Factors in Two Argentine Settings

2022-02-15T20:05:57Z

Preprint Journal of Cancerology; 2015, no. 2 Objectives: The purpose of this study was to compare risk and prognostic factors of invasive breast cancer in two Argentine populations. Patients and Methods: a total of 625 women with invasive breast cancer at different stages were studied: 270 patients from the city of La Plata, and 355 patients from the city of Neuquén. Demographic features and reproductive history were considered as risk factors, while prognostic factors included histopathological features. Statistical analysis was performed. Results: The age at diagnosis was significantly lower in Neuquén than in La Plata; stage III was observed in La Plata at a mean age of 49 years versus 54 years in Neuquén; cutaneous and/or thoracic wall invasion was found at diagnosis in Neuquén, while it was absent in all La Plata patients. Tumor size versus age showed a negative statistical significant relationship; the percentage of HER2/neu-positives in Neuquén was significantly higher than in La Plata, while estrogen/progesterone receptor status showed the contrary. Histological and nuclear grades in Neuquén compared to La Plata were significantly higher, while vascular invasion showed the converse. Considering the number of children, significant differences between groups were found, and also, patients who had breastfed presented a lower number of metastatic lymph nodes than those who had not. Conclusions: La Plata and Neuquén constitute two different populations. The factors that contribute to dividing the groups could be related to the malignant histological characteristics of the tumors, but also the length of breastfeeding and number of children could play a role.

MUC1 oncogene amplification correlates with protein overexpression in invasive breast carcinoma cells

2021-11-30T20:05:47Z

Articulo Cancer Genetics and Cytogenetics; vol. 201, no. 2 The MUC1 gene is aberrantly overexpressed in approximately 90% of human breast cancers. Several studies have shown that MUC1 overexpression is due to transcriptional regulatory events. However, the importance of gene amplification as a mechanism leading to the increase of MUC1 expression in breast cancer has been poorly characterized. The aim of this study was to evaluate the role of MUC1 gene amplification and protein expression in human breast cancer development. By means of real-time quantitative polymerase chain reaction and immunohistochemical methods, 83 breast tissue samples were analyzed for MUC1 gene amplification and protein expression. This analysis showed MUC1 genomic amplification and a positive association with the histopathological group in 12% (1 out of 8) of benign lesions and 38% (23 out of 60) of primary invasive breast carcinoma samples (P = 0.004). Array-comparative genomic hybridization meta-analysis of 886 primary invasive breast carcinomas obtained from 22 studies showed MUC1 genomic gain in 43.7% (387 out of 886) of the samples. Moreover, we identified a highly statistical significant association between MUC1 gene amplification and MUC1 protein expression assessed by immunohistochemistry and Western blot test (P < 0.0001). In conclusion, this study demonstrated that MUC1 copy number increases from normal breast tissue to primary invasive breast carcinomas in correlation with MUC1 protein expression.