Differences in the expression of the phosphatase PTP-1B in patients with localized prostate cancer with and without adverse pathological features.

Introduction: Patients with adverse pathological features (APF) at radical prostatectomy (RP) for prostate cancer (PC) are candidates for adjuvant treatment. Clinicians lack reliable markers to predict these APF preoperatively. Protein tyrosine phosphatase 1B (PTP-1B) is involved in migration and invasion of PC, and its expression could predict presence of APF. Our aim was to compare PTP-1B expression in patients with and without APF, and to explore PTP-1B expression as an independent prognostic factor. Methods: Tissue microarrays (TMAs) were constructed using RP archival specimens for immunohistochemical staining of PTP-1B; expression was reported with a standardized score (0-9). We compared median PTP-1B score between cases with and without APF. We constructed two logistic regression models, one to identify the independence of PTP-1B score from biologically associated variables (metformin use and type 2 diabetes mellitus [T2DM]) and the second to seek independence of known risk factors (Gleason score and prostate specific antigen [PSA]). Results: A total of 73 specimens were suitable for TMA construction. Forty-four (60%) patients had APF. The median PTP-1B score was higher in those with APF: 8 (5-9) vs 5 (3-8) (p=0.026). In the logistic regression model including T2DM and metformin use, the PTP-1B score maintained statistical significance (OR 1.21, 95% CI 1.01-1.45, p=0.037). In the model including PSA and Gleason score; the PTP-1B score showed no independence (OR 1.68, 95% CI 0.97-1.41, p=0.11). The area under the curve to predict APF for the PTP-1B score was 0.65 (95% CI 0.52-0.78, p=0.03), for PSA+Gleason 0.71 (95% CI 0.59-0.82, p=0.03), and for PSA+Gleason+PTP-1B score 0.73 (95% CI 0.61-0.84, p=0.001). Discussion: Patients with APF after RP have a higher expression of PTP-1B than those without APF, even after adjusting for T2DM and metformin exposure. PTP-1B has a good accuracy for predicting APF but does not add to known prognostic factors.

Vaccination status and attitudes towards COVID-19 vaccination in patients undergoing active cancer treatment in a referral center in Mexico: a survey study.

BACKGROUND: COVID-19 vaccination refusal/hesitancy among patients with cancer has been reported to be high. This study aimed to assess vaccination status and attitudes towards COVID-19 vaccines in patients with cancer undergoing active treatment in a single center in Mexico. METHODS: A cross-sectional, 26-item survey evaluating vaccination status and attitudes towards COVID-19 vaccination was conducted among patients undergoing active cancer treatment. Descriptive statistics were used to analyze the sociodemographic characteristics, vaccination status, and attitudes. X2 tests and multivariate analysis were used to evaluate associations between characteristics and attitudes with adequate vaccination status. RESULTS: Of 201 respondents, 95% had received at least one dose, and 67% had adequate COVID-19 vaccination status (≥ 3 doses). Thirty-six percent of patients had at least one reason for doubting/rejecting vaccination, and the main reason was being afraid of side effects. On multivariate analysis, age ≥ 60 years (odds ratio (OR) 3.77), mass media as main source of information on COVID-19 (OR 2.55), agreeing vaccination against COVID-19 is safe in patients with cancer (OR 3.11), and not being afraid of the composition of the COVID-19 vaccines (OR 5.10) statistically increased the likelihood of adequate vaccination status. CONCLUSIONS: Our study shows high vaccination rates and positive attitudes towards COVID-19 vaccines, with a significant proportion of patients undergoing active cancer treatment with adequate vaccination status (≥ 3 doses). Older age, use of mass media as main source of COVID-19 information, and positive attitudes towards COVID-19 vaccines were significantly associated with a higher likelihood of adequate COVID-19 vaccination status among patients with cancer.

Paclitaxel resistance is mediated by NF-κB on mesenchymal primary breast cancer cells.

Paclitaxel has been used widely to treat breast cancer and other types of cancer. However, resistance is a major cause of failure for treatment and results in cancer progression. The present study investigated the association between paclitaxel resistance and the mesenchymal phenotype, using a model of primary breast cancer cells and employing four different cultures, two with an epithelial phenotype (MBCDF and MBCD17) and two with a mesenchymal phenotype (MBCDF-D5 and MBCD3). Epithelial-mesenchymal markers were evaluated by western blotting; MBCDF and MBCD17 cells expressed E-cadherin, SNAIL, Slug, and Twist, low levels of N-cadherin, but not vimentin. MBCDF-D5 and MBCD3 cells expressed N-cadherin, vimentin, and higher levels of SNAIL, and low levels of E-cadherin, Slug, and Twist. Cell viability was evaluated using a crystal violet assay after paclitaxel treatment; primary breast cancer cells with mesenchymal phenotype were resistant to paclitaxel compared with the epithelial primary breast cancer cells. Furthermore, using western blotting, it was revealed that mesenchymal cells had elevated levels of nuclear factor-κΒ (NF-κB) p65 and IκB kinase (IKK). Additionally, it was demonstrated that paclitaxel-induced degradation of the inhibitor of NF-κB, activation of NF-κB in a dose-dependent manner, and Bcl-2 and Bcl-xL upregulation. Finally, employing western blotting and crystal violet assays, the effects of the proteasome inhibitor ALLN were assessed. ALLN inhibited paclitaxel-induced NF-κB activation and restored the sensitivity to paclitaxel. Together, these data suggest that targeting the NF-κB/IKK axis might be a promising strategy to overcome paclitaxel resistance.

Conditioning Regimens in Allogeneic Hematopoietic Stem Cell Transplantation Do Not Fit All: Adjusting BuCy2 in Mexico to Improve Outcomes in Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS).

Background: Conditioning regimens are critical for allogeneic hematopoietic cell transplantation (allo-HCT). After unfavorable results using BuCy2 at the beginning of our HCT Program, a restructuring was made with the consequent development of a modified HCT method including a reduced conditioning regimen. The objective of this study was to describe the outcomes using Reduced BuCy2 (rBuCy2) in allo-HCT. Materials and Methods: Data from 38 consecutive patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) who underwent allo-HCT conditioned with rBuCy2 in a 21-year period were retrospectively analyzed. Results: Most patients were males (53%) and the median age was 35 years. The most common disease was myelodysplastic syndrome (55%). Toxicity grades III-IV were observed in 44%; and acute and chronic graft-versus-host disease were observed in 26% and 34%, respectively; the median follow-up was 26 months; 30-day non-relapse mortality (NRM) was 3%, and 1 and 2-year NRM were 8%. Ten-year overall survival (OS) was 60%, and 86%, for AML and MDS, respectively. Conclusion: Our rBuCy2 maintains a myeloablative effect, along with immunosuppression for fast engraftment and more importantly, this regimen reduces grades III-IV acute GVHD and NRM in allo-HCT and improves the OS and it appears to be an option for low and middle-income countries.

Do circulating neutrophil extracellular traps predict recurrence in early breast cancer?

Background: Neutrophil extracellular traps (NETs), three-dimensional structures formed by neutrophil enzymes such as neutrophil elastase (NE) and nuclear components (DNA), have been associated with progression and metastasis in breast cancer (BC). Thus, the aim of this study was to evaluate the association of circulating NETs with clinicopathological characteristics and outcomes in early BC. Methods: A prospective cohort included women with newly diagnosed early BC. NETs were defined as the presence of NE-DNA complexes in plasma, measured by optical density. Levels of NETs were dichotomized according to the median, as low and high levels of circulating NETs. Fisher's exact test was used to evaluate associations between NETs and clinicopathological characteristics and outcomes. Survival was assessed using the Kaplan Meier method and log-rank test. Results: Forty patients were included, 23 (57.5%) patients with low and 17 (42.5%) with high levels of circulating NETs. No associations were found between clinicopathological characteristics and circulating NETs levels. Recurrence (p = 0.99) and site of recurrence (p = 0.99) were not statistically associated with plasma NETs levels. Overall, recurrence-free survival was not statistically different between circulating levels of NETs. Conclusions: With a short follow-up and low number of events, our results suggest that circulating levels of NETs at diagnosis of early BC are not associated with more aggressive clinicopathological characteristics, recurrence, or site of recurrence.

Predominant low Hematopoietic Cell Transplantation Specific Comorbidity Index (HCT-CI) score in a Mexican referral center: a selection bias caused by limited-resources?

Abstract Introduction: To date, many studies have validated the Hematopoietic Cell Transplantation Specific Comorbidity Index (HCT-CI) scoring system in allogeneic hematopoietic stem cell transplantation (allo-HSCT), but studies from developing countries remain scarce. Objective: The aim of this study was to evaluate and categorize Mexican patients using the HCT-CI at a referral center. Methods: One hundred and nineteen consecutive patients undergoing allo-HSCT at the National Institute of Medical Sciences and Nutrition in Mexico City were included. Patients were classified according to the HCT-CI scores. Results: The median age was 31 years and most were males (56%). Most patients had hematological malignancies (73%) and a low HCT-CI score (72%). The non-relapse mortality and survival were predicted according to the score. Conclusions: This is one of the few studies to evaluate the HCT-CI in adults with HLA-matched donors in a developing country and our findings suggest that the high percentage of patients with a low HCT-CI scores, contrary to international reports, could be explained by different comorbidities and demographics, but mainly due to stricter filters applied to HSCT candidates and consequently, a potential selection bias caused by limited resources.

Predominant low Hematopoietic Cell Transplantation Specific Comorbidity Index (HCT-CI) score in a Mexican referral center: a selection bias caused by limited-resources?

INTRODUCTION: To date, many studies have validated the Hematopoietic Cell Transplantation Specific Comorbidity Index (HCT-CI) scoring system in allogeneic hematopoietic stem cell transplantation (allo-HSCT), but studies from developing countries remain scarce. OBJECTIVE: The aim of this study was to evaluate and categorize Mexican patients using the HCT-CI at a referral center. METHODS: One hundred and nineteen consecutive patients undergoing allo-HSCT at the National Institute of Medical Sciences and Nutrition in Mexico City were included. Patients were classified according to the HCT-CI scores. RESULTS: The median age was 31 years and most were males (56%). Most patients had hematological malignancies (73%) and a low HCT-CI score (72%). The non-relapse mortality and survival were predicted according to the score. CONCLUSIONS: This is one of the few studies to evaluate the HCT-CI in adults with HLA-matched donors in a developing country and our findings suggest that the high percentage of patients with a low HCT-CI scores, contrary to international reports, could be explained by different comorbidities and demographics, but mainly due to stricter filters applied to HSCT candidates and consequently, a potential selection bias caused by limited resources.

Patient Navigation to Improve Early Access to Supportive Care for Patients with Advanced Cancer in Resource-Limited Settings: A Randomized Controlled Trial.

BACKGROUND: The early integration of supportive care in oncology improves patient-centered outcomes. However, data are lacking regarding how to achieve this in resource-limited settings. We studied whether patient navigation increased access to multidisciplinary supportive care among Mexican patients with advanced cancer. MATERIALS AND METHODS: This randomized controlled trial was conducted between August 2017 and April 2018 at a public hospital in Mexico City. Patients aged ≥18 years with metastatic tumors ≤6 weeks from diagnosis were randomized (1:1) to a patient navigation intervention or usual care. Patients randomized to patient navigation received personalized supportive care from a navigator and a multidisciplinary team. Patients randomized to usual care obtained supportive care referrals from treating oncologists. The primary outcome was the implementation of supportive care interventions at 12 weeks. Secondary outcomes included advance directive completion, supportive care needs, and quality of life. RESULTS: One hundred thirty-four patients were randomized: 67 to patient navigation and 67 to usual care. Supportive care interventions were provided to 74% of patients in the patient navigation arm versus 24% in usual care (difference 0.50, 95% confidence interval [CI] 0.34-0.62; p < .0001). In the patient navigation arm, 48% of eligible patients completed advance directives, compared with 0% in usual care (p < .0001). At 12 weeks, patients randomized to patient navigation had less moderate/severe pain (10% vs. 33%; difference 0.23, 95% CI 0.07-0.38; p = .006), without differences in quality of life between arms. CONCLUSION: Patient navigation improves access to early supportive care, advance care planning, and pain for patients with advanced cancer in resource-limited settings. IMPLICATIONS FOR PRACTICE: The early implementation of supportive care in oncology is recommended by international guidelines, but this might be difficult to achieve in resource-limited settings. This randomized clinical trial including 134 Mexican patients with advanced cancer demonstrates that a multidisciplinary patient navigation intervention can improve the early access to supportive and palliative care interventions, increase advance care planning, and reduce symptoms compared with usual oncologist-guided care alone. These results demonstrate that patient navigation represents a potentially useful solution to achieve the adequate implementation of supportive and palliative care in resource-limited settings globally.

Overcoming barriers for the establishment of a consolidated hematopoietic cell transplantation program in a developing country.

The first hematopoietic cell transplantation (HCT) in Mexico was performed at our institution; however, outcomes were suboptimal the following years, until 1998, when a consolidated HCT was established. The aim of this study was to describe the barriers and the implemented strategies to establish a successful HCT program at a referral center in Mexico and to analyze the outcomes. Barriers were detected based on the results from 1980 to 1997. For the analysis of outcomes, a retrospective study was performed including consecutive patients undergoing autologous, allogeneic, and haploidentical HCT. From November 1998 to December 2018, 363 HCTs were performed (autologous, 59%) in 323 patients. Overall non-relapse mortality (NRM) in autologous and allogeneic HCT was 2% and 14%, respectively. The 5-year overall survival was 71% and 57% for autologous and allogeneic HCT, respectively. The cost of the medications was one of the main limitations for the patients and was successfully overcome by the creation of the non-governmental organization "Unidos". NRM was diminished after reducing the BuCy2 regimen along with the use of bone marrow. Our results highlight that the implementation of unique strategies at our center, led HCT to represent a financially viable and feasible procedure with optimal results.

Infections after hematopoietic cell transplantation are not a burden for mortality at a limited-resource center in a developing country.

BACKGROUND: Hematopoietic cell transplantation (HCT) outcomes, including infectious complications, change between centers and countries. Thus, the aim of this study was to report the incidence of infections and isolated pathogens among recipients of HCT and the association with mortality at a tertiary referral center in Mexico. METHODS: Two hundred and eighty-two patients undergoing autologous or allogeneic HCT between January 2005 and December 2018 at the National Institute of Medical Sciences and Nutricion Salvador Zubiran were included. RESULTS: In autologous HCT (n = 176), within the preengraftment and the early postengraftment, 130 (74%) and 31 (18%) recipients presented infections, respectively. Within the preengraftment, the early postengraftment, and the late postengraftment, 81 (76%), 34 (33%), and 58 (60%) allogeneic HCT recipients presented infections, respectively. Non-relapse mortality (NRM) as a result of infections occurred in 1 (0.6%) and 5 (5%) autologous and allogeneic HCT recipients, respectively. CONCLUSIONS: Our results demonstrated that despite our limited resources, infections were not a significant burden for NRM among HCT recipients. More importantly, the isolation rates were higher than international studies, which could be explained by the existence of a specialized infectious diseases department and laboratory, which we consider key elements for the establishment of an HCT program worldwide.

Building a hematopoietic cell transplantation outcomes registry in Mexico.

The aim of this study was to assess the feasibility of hematopoietic cell transplantation (HCT) data collection using an electronic platform at Mexican centers. Four public centers performing HCT in adults were included. A cloud-based electronic platform in Spanish was developed to allow real-time registration of demographic, clinical, and outcomes variables. Data were obtained from paper and electronic medical records and institutional databases. Data managers were hired to perform the collection. Data from January 2015 to December 2018 were retro and prospectively collected during a 10-month period. From 2015 to 2018, 473 HCT were performed. Most were autologous (55%). Patients undergoing autologous HCT had the highest median age (49 years) compared with patients undergoing allogeneic (34 years) or haploidentical HCT (29 years). The most common underlying disease for autologous HCT was multiple myeloma. Acute leukemias were the most common diagnoses among allogeneic and haploidentical HCT recipients. Two-year nonrelapse mortality was 2.5%, 18%, and 18% for autologous, allogeneic, and haploidentical HCT, respectively. We determined it was feasible to start a multicenter collaborative study in Mexico as it was very well received by the physicians and it can lead to the creation of a Mexican HCT Registry in the near future.

Neutrophil Extracellular Traps Associate with Clinical Stages in Breast Cancer.

Recently, neutrophil extracellular traps (NETs), three-dimensional structures formed of neutrophil enzymes such as neutrophil elastase (NE) and nuclear components (DNA), have been associated with progression in different types of cancer. However, data remain scarce in breast cancer. Thus, the aim of this study was to associate NETs with clinical stages of breast cancer. A prospective analysis was performed in 45 plasma samples of female patients with newly diagnosed breast cancer. NE-DNA complexes were evaluated by ELISA. Optical density was dichotomized at the median for comparisons (low and high levels of NE-DNA). The most frequent clinical stage was localized (n = 28, 62%) followed by regional (n = 13, 29%) and distant (n = 4, 9%). Higher levels of NE-DNA complexes were observed in regional and distant stages compared to localized disease (68% vs 32%, p = 0.034). No differences were observed when comparing other clinical characteristics between both groups. We demonstrated that the levels of NETs increase in proportion to the stage of the disease, observing higher levels of NE-DNA complexes in regional and metastatic disease, which coincides with the proposed mechanism by which cancer progression and metastasis might result from the formation of NETs.

Correlation of T Cell Subsets and Hypercholesterolemia of the Donor and Its Association with Acute Graft-versus-Host Disease.

Background: Acute graft-versus-host disease (aGVHD) is an important cause of death following allogeneic hematopoietic stem cell transplantation (allo-HSCT). The association between cholesterol and aGVHD was previously described potentially, resulting from pro-inflammatory responses associated with hypercholesterolemia. The aim of this study was to correlate T cell subsets in donor bone marrow (BM) samples with their levels of cholesterol and associate these results with recipients who developed aGVHD and those who did not. Materials and Methods: A prospective study was performed in 39 donor samples. T cell subsets were analyzed by flow cytometry. Results: Eleven (28%) donors had hypercholesterolemia. Donor samples with hypercholesterolemia had less Tregs compared to donors with normal levels of cholesterol (22.69 (IQR=30.6) cells/µL vs 52.62 (IQR=44.68) cells/µL, p=0.04). Among all individuals in the cohort, aGVHD was observed in 21%: 36% from donors with hypercholesterolemia versus 14% from donors with normal levels of cholesterol. Conclusion: As we described the association between hypercholesterolemia and diminished Tregs, our results might suggest that normalizing the levels of total cholesterol in the donor, prior performing allo-HSCT, might be an effective approach to diminish the risk of the receptor to develop aGVHD.

COULD NEUTROPHIL EXTRACELLULAR TRAPS BE THE NEW PROGNOSTIC MARKERS OF CANCER?

Neutrophil extracellular traps (NETs) were described more than one decade ago, but recently, the interest in these structures has increased due to their involvement in cancer progression, cancer-related thrombosis, and development of metastasis. This protumoral role of NETs strengthens their potential as new prognostic markers of cancer.

Could neutrophil extracellular traps be the new prognostic markers of cancer?

ABSTRACT Neutrophil extracellular traps (NETs) were described more than one decade ago, but recently, the interest in these structures has increased due to their involvement in cancer progression, cancer-related thrombosis, and development of metastasis. This protumoral role of NETs strengthens their potential as new prognostic markers of cancer.

Association of Outcomes and Socioeconomic Status in Mexican Patients Undergoing Allogeneic Stem Cell Transplantation.

The association of clinical outcomes after hematopoietic stem cell transplantation (HSCT) with the patient's socioeconomic status (SES) remains controversial, with the majority of studies reported to date performed in developed countries. Data from low- and middle-income regions where the SES varies greatly remain scarce. The objective of this study was to associate SES with outcomes after allogeneic HSCT in a referral center in Mexico. A retrospective study was performed including 124 consecutive patients. Patients were dichotomized into 2 groups based on a consensus with the Department of Social Work: low SES (level I-II) and high SES (level ≥III). Most patients were of low SES (n = 84; 68%). Age, educational attainment, employment status, and financial support were the sociodemographic characteristics that statistically differed between the 2 groups. All patients with low SES received financial support from governmental agencies or nongovernmental organizations (NGOs). Nonrelapse mortality and overall survival were similar in the 2 groups. Our study found no statistically significant differences in survival outcomes between patients of low SES and high SES. This demonstrates that our HSCT approaches are standardized and that all patients can benefit from HSCT irrespective of their financial status. It also suggests that the good outcomes in patients with low SES probably are related to the substantial governmental, NGO, and/or institutional subsidies these patients receive.