Publications by authors named "Wilson Golomar"

7 Publications

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Dietary acid load and lung cancer risk: A case-control study in men.

Cancer Treat Res Commun 2021 Apr 25;28:100382. Epub 2021 Apr 25.

Unit of Thoracic Oncology, National Cancer Institute, Joanicó 3265, Montevideo 11600, Uruguay.

Background: Dysregulation of the endogenous acid-base balance can contribute to inflammation and cancer development if metabolic acidosis is sustained. The epidemiologic evidence on the association between diet-dependent acid load and cancer risk is scarce and inconsistent. We aim to explore the possible role of dietary acid load in lung cancer (LC) risk.

Methods: A case-control study was performed on 843 LC cases and 1466 controls by using a multi-topic questionnaire, including a food frequency questionnaire. Controls were matched to cases by age-frequency, urban/rural residence, and region. Food-derived nutrients were calculated from available databases. The dietary acid load was calculated using validated measures as potential renal acid load (PRAL) score and net endogenous acid production (NEAP) score. Odds ratios (ORs) were estimated by logistic regression.

Results: We found direct associations between dietary acid load and LC risk. The highest quartile of the NEAP score was significantly associated (OR=2.22, p<0.001). The PRAL score displayed similar associations in simpler regression models, but there was no association when a more complex one was used (OR=0.99, p =0.94). The NEAP score was associated with a significant risk increase in all cell types, except for small cell cancers, but the PRAL score did not show any association.

Conclusions: The NEAP scores, directly associated with meat intake and inversely associated with plant-based foods intake, suggest that a high acid load dietary style may increase LC risk. Studies focused on food groups, and nutritional patterns are in line with our findings. Although the data shown here represent the first one to be published on this issue, further studies are needed to confirm these findings.
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http://dx.doi.org/10.1016/j.ctarc.2021.100382DOI Listing
April 2021

Addition of an induction regimen of antiangiogenesis and antitumor immunity to standard chemotherapy improves survival in advanced malignancies.

Med Oncol 2012 Dec 19;29(5):3626-33. Epub 2012 Jul 19.

Interdoctors Network, Montevideo, Uruguay.

Studies have shown that cancer requires two conditions for tumor progression: cancer cell proliferation and an environment permissive to and conditioned by malignancy. Chemotherapy aims to control the number and proliferation of cancer cells, but it does not effectively control the two best-known conditions of the tumor-permissive environment: neoangiogenesis and tolerogenic immunity. Many malignant diseases exhibit poor outcomes after treatment with chemotherapy. Therefore, we investigated the potential benefits of adding an induction regimen of antiangiogenesis and antitumor immunity to chemotherapy in poor outcome disease. In a prospective, randomized trial, we included patients with advanced, unresectable pancreatic adenocarcinomas, non-small cell lung cancer, or prostate cancer. Two groups of each primary condition were compared: group 1 (G1), n = 30, was treated with the standard chemotherapy and used as a control, and group 2 (G2), n = 30, was treated with chemotherapy plus an induction regimen of antiangiogenesis and antitumor immunity. This induction regimen included a low dose of metronomic cyclophosphamide, a high dose of Cox-2 inhibitor, granulocyte colony-stimulating factor, a sulfhydryl (SH) donor, and a hemoderivative that contained autologous tumor antigens released from patient tumors into the blood. After treatment, the G2 group demonstrated significantly longer survival, lower blood level of neoangiogenesis and immune-tolerance mediators, and higher blood levels of antiangiogenesis and antitumor immunity mediators compared with the G1 group. Toxicity and quality of life were not significantly different between the groups. In conclusion, in several advanced malignancies of different primary localizations, an increase in survival was observed by adding an induction regimen of antiangiogenesis and antitumor immunity to standard chemotherapy.
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http://dx.doi.org/10.1007/s12032-012-0301-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3505507PMC
December 2012

Advanced breast cancer: anti-progressive immunotherapy using a thermostable autologous hemoderivative.

Breast Cancer Res Treat 2006 Nov 4;100(2):149-60. Epub 2006 Jul 4.

PharmaBlood Inc, Research & Development Department, 2050 NE 163rd Street, # 202, North Miami Beach, Florida 33162, USA.

Introduction: Advanced breast cancer patients, acquired-chemotherapy resistant and in progression, are therapeutically terminal. We tested a recently described medical procedure using a thermostable autohemoderivative purported to inhibit tumor growth possibly through an immunological mechanism of action.

Patients And Methods: Metastatic breast cancer patients, chemotherapy-resistant, high CEA and CA 15-3 plasma levels of tumor markers, in progression, were 2-group randomized. Group 1 received the test procedure and Group 2 adequate measures to be comparable control. From 121 included patients, 108 could be evaluated. During 8-month follow-up period, tumor growth, number of cases attaining clinical non-progressive status and mortality were monthly assessed. Immunologic effect was assessed by delayed type hypersensitivity test and lymphocyte proliferation assay. Responding-tumors histopathologies were studied. The proteome of the autologous immunogen was characterized by 2-D electrophoresis.

Results And Discussion: In a significant number of cases, the test procedure promoted inhibition of tumor growth, non-progressive disease status, and lower cumulative mortality. These clinical results were associated with polyvalent immunization against several tested antigens: the hemoderivative used for treatment, the blood tumor markers and the derivative obtained from a regulatory lymphocyte population (CD4+CD25+). Interference with this regulatory activity could explain the selective autoimmunity suggested by the histopathology findings in responding tumors. The thermostability could be an essential property of the immunogen hemoderivative.

Conclusion: The thermostable autohemoderivative tested is antigenically polyvalent and promoted a polytargeted immune response associated to a tumor anti-progressive effect, consequently, acting as an autohemoderivative cancer vaccine.
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http://dx.doi.org/10.1007/s10549-006-9235-7DOI Listing
November 2006

Advanced colon cancer: antiprogressive immunotherapy using an autologous hemoderivative.

Med Oncol 2006 ;23(1):91-104

Department of Research & Development, PharmaBlood Inc, 2050 NE 163rd Street, # 202, North Miami Beach, Florida 33162, USA.

Introduction: Advanced colon cancer patients, acquired-chemotherapy resistant and in progression, are therapeutically terminal. We tested a recently described medical procedure using a thermostable autologous hemoderivative purported to inhibit tumor growth possibly through an immunological mechanism of action.

Patients And Methods: Metastatic colon cancer patients chemotherapy-resistant, high CEA plasma levels, in progression, were 2-group randomized. Group 1 received the test procedure and Group 2 adequate control measures. During an 8-mo follow-up period (n = 101), tumor growth, number of cases attaining clinical nonprogressive status, and mortality were assessed monthly. Immunological effect was assessed by delayed-type hypersensitivity test and lymphocyte proliferation assay. Responding-tumors histopathologies were studied.

Results And Discussion: In a significant number of cases, the test procedure promoted inhibition of tumor growth, nonprogressive disease status, and lower cumulative mortality. These clinical results were associated with polyvalent immunization against several tested antigens: the hemoderivative used for treatment, the blood tumor markers, and the regulatory lymphocyte population (CD4+CD25+). Interference with this regulatory activity could explain the selective autoimmunity suggested by the histopathology findings in responding tumors.

Conclusion: The autologous hemoderivative tested is antigenically polyvalent and promotes a polytargeted immune response associated with a tumor antiprogressive effect, consequently, acting as an autologous hemoderivative cancer vaccine.
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http://dx.doi.org/10.1385/mo:23:1:91DOI Listing
June 2006

Insulin-induced enhancement of antitumoral response to methotrexate in breast cancer patients.

Cancer Chemother Pharmacol 2004 Mar 4;53(3):220-4. Epub 2003 Dec 4.

Department of Medicine, School of Medicine, University of Uruguay, Montevideo, Uruguay.

Purpose: It has been reported that insulin increases the cytotoxic effect in vitro of methotrexate by as much as 10,000-fold. The purpose of this study was to explore the clinical value of insulin as a potentiator of methotrexate.

Patients And Methods: Included in this prospective, randomized clinical trial were 30 women with metastatic breast cancer resistant to fluorouracil + Adriamycin + cyclophosphamide and also resistant to hormone therapy with measurable lesions. Three groups each of ten patients received two 21-day courses of the following treatments: insulin + methotrexate, methotrexate, and insulin, respectively. In each patient, the size of the target tumor was measured before and after treatment according to the Response Evaluation Criteria In Solid Tumors. The changes in the size of the target tumor in the three groups were compared statistically.

Results: Under the trial conditions, the methotrexate-treated group and the insulin-treated group responded most frequently with progressive disease. The group treated with insulin + methotrexate responded most frequently with stable disease. The median increase in tumor size was significantly lower with insulin + methotrexate than with each drug used separately.

Discussion: Our results confirmed in vivo the results of previous in vitro studies showing clinical evidence that insulin potentiates methotrexate under conditions where insulin alone does not promote an increase in tumor growth. Therefore, the chemotherapy antitumoral activity must have been enhanced by the biochemical events elicited in tumor cells by insulin.

Conclusions: In multidrug-resistant metastatic breast cancer, methotrexate + insulin produced a significant antitumoral response that was not seen with either methotrexate or insulin used separately.
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http://dx.doi.org/10.1007/s00280-003-0716-7DOI Listing
March 2004

Antitumoral effect of a vaccination procedure with an autologous hemoderivative.

Cancer Biol Ther 2003 Mar-Apr;2(2):155-60

School of Medicine, University of Uruguay, Uruguay.

Lately, the promising results obtained with autologous cancer vaccines are stimulating new research in the old field of cancer immunotherapy. This paper describes the development of a procedure previously reported by us that is used to obtain an autologous hemoderivative with antitumoral properties. The procedure has been tested in a phase I-II, randomized, controlled clinical trial of 28 cancer patients with different primary malignancies in metastatic and chemotherapy-resistant stages. The histology of the lesions that responded to this treatment was consistent with the characteristic histology observed in malignant lesions treated with a similar antitumoral hemoderivative: proliferation of stromal connective tissue, T-lymphocyte infiltration, and a reduction in the amount of tumor cells and blood vessels. We concluded that vaccination had elicited an immune response because a delayed-type hypersensitivity test made with the autologous hemoderivative produced a significantly more intense response in the responding treated patients. We propose that an immune mechanism acting on tumor cells and/or the regulatory system for stromal growth explains the histological results observed. The use of blood to obtain the immunogen allows vaccination to be repeated, so this method could avoid tumor escape responses due to mutations in the antigen library of the tumor. The results of our study justify further research to optimize the antitumoral effect of vaccination.
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http://dx.doi.org/10.4161/cbt.2.2.247DOI Listing
October 2003

Serum markers variation consistent with autoschizis induced by ascorbic acid-menadione in patients with prostate cancer.

Med Oncol 2003 ;20(1):45-52

School of Medicine, University of Uraguay, Montevideo, Uriguay.

In vitro exposure of malignant prostate cell lines to ascorbic acid-menadione showed that tumor cells were killed through a mechanism named autoschizis. Experimental animal studies showed that autoschizis is also evident when ascorbic acid-menadione is administered to nude mice with implanted human prostate tumors. Prostate-specific antigen (PSA) is a known serum marker of prostate tumor cells specific activity. Recently, total serum homocysteine has been identified as a marker of tumor cell numbers with sensitivity for early detection of tumor cell death induced by treatments. A clinical trial with prostate cancer patients submitted to the association of ascorbic acid-menadione was performed and PSA/homocysteine was assessed in the follow- up. The early response in serum PSA and homocysteine levels was reported. The results showed that ascorbic acid-menadione produced an immediate drop in tumor cell numbers as assessed by homocysteine levels. Serum PSA levels showed an early rise and later dropped. These results suggest that autoschizis can also be induced by this pharmacological association at the clinical level in prostate cancer patients. Further studies are being performed in order to research if these results can be found with other primary tumors as it was shown in in vitro and experimental models. Ascorbic acid-menadione could be emerging as a new antitumoral chemotherapy.
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http://dx.doi.org/10.1385/mo:20:1:45DOI Listing
October 2003