Sergio Rodríguez-Cuevas

Carotid body tumors in inhabitants of altitudes higher than 2000 meters above sea level

Carotid body tumors (CBTs) are rare. Diagnosis is usually delayed until the tumors reach a critical volume and a mass appears in the neck, which is often asymptomatic.

Electrochemotherapy in Primary and Metastatic Skin Tumors: Phase II Trial Using Intralesional Bleomycin

BACKGROUND Surgery and/or radiotherapy are the elective therapies for most primary skin cancers. Nevertheless, some patients develop recurrences, and chemotherapy has resulted in poor complete responses. Permeabilization of the cell membrane by electric pulses allows bleomycin to enter into the cell, increasing possibility of cytotoxicity. METHODS From November 1998 through November 1999, 15 patients with 38 skin lesions participated in a phase II prospective clinical trial, using intralesional bleomycin plus electric pulses delivered 10 min after bleomycin injection, which lasted 100 microsec each at field strength of 1,300 V/cm and a frequency of 1 Hz. There were basal cell carcinomas (BCC) (nine lesions), in-transit metastasis of melanoma (MM) (two patients/13 nodules), squamous cell carcinomas (SCC) of the upper aerodigestive tract metastatic to the skin (two patients/two nodules), and skin metastases from breast cancer (two patients/14 nodules). Mean follow-up was 8.6 months. RESULTS Overall objective responses were 98%, with complete responses achieved in 49%, partial responses in 49%, and no responses in 2%. No complications were documented related to the treatment and tolerance was adequate. CONCLUSIONS Electrochemotherapy (ECT) is a new cancer modality of treatment that is effective in a variety of skin cancers. This treatment represents an excellent alternative to standard surgery or radiotherapy, with an outpatient-based treatment applied in one to three sessions. The major impact was obtained in BBC, but ECT is a useful palliative therapy in melanoma, breast cancer, or SCC. More experience and longer follow-up are required to determine long-term results.

First Breast Cancer Mammography Screening Program in Mexico: Initial Results 2005–2006

Abstract:  Breast cancer is the most frequent malignant neoplasia worldwide. In emergent countries as Mexico, an increase has been shown in frequency and mortality, unfortunately, most cases in advanced loco‐regional stages developed in young women. The success of breast screening in mortality reduction has been observed since 1995 in Western Europe and the United States, where as many as 40% mortality reduction has been achieved. Most countries guidelines recommends an annual or biannual mammography for all women >40 years of age. In 2005, FUCAM, a nonlucrative civil foundation in Mexico join with Mexico City government, initiated the first voluntary mammography screening program for women >40 years of age residing in Mexico City’s Federal District. Mammographies were carried out with analogical mammographs in specially designed mobile units and were performed in the area of women’s domiciles. This report includes data from the first 96,828 mammographies performed between March 2005 and December 2006. There were 1% of mammographies in Breast Imaging Reporting and Data System 0, 4, or 5 and 208 out of 949 women with abnormal mammographies (27.7%) had breast cancer, a rate of 2.1‰, most of them in situ or stage I (29.4%) or stage II (42.2%) nevertheless 21% of those women with abnormal mammography did not present for further clinical and radiologic evaluation despite being personally notified at their home addresses. The breast cancer rate of Mexican women submitted to screening mammography is lower than in European or North American women. Family history of breast cancer, nulliparity, absence of breast feeding, and increasing age are factors that increase the risk of breast cancer. Most cancers were diagnosed in women’s age below 60 years (68.5%) with a mean age of 53.55 corroborating previous data published. It is mandatory to sensitize and educate our population with regard to accepting to visit the Specialized Breast Centers.

Evolution of maxillofacial brown tumors after parathyroidectomy in primary hyperparathyroidism

Brown tumor occasionally affects the facial bones. Clinically, these lesions can be mistaken for a neoplasm. Opinions are divided on the course of management of the bony lesions once parathyroidectomy has been carried out.

Determination of the protein expression profiles of breast cancer cell lines by quantitative proteomics using iTRAQ labelling and tandem mass spectrometry.

UNLABELLED Breast cancer is the principal cancer in women worldwide. Although there are serum tumor markers such as CEA and HER2, they are detected in advanced stages of the disease and used as progression and recurrence markers. Therefore, there is a necessity for the identification of new markers that might lead to an early detection and also provide evidence of an effective treatment. The aim of this work was to determine the differential protein expression profiles of four breast cancer cell lines in comparison to a normal control cell line by iTRAQ labelling and tandem mass spectrometry, in order to identify putative biomarkers of the disease. We identified 1,020 iTRAQ-labelled polypeptides with at least one peptide identified with more than 95% in confidence. Overexpressed polypeptides in all cancer cell lines were 78, whilst the subexpressed were 128. We categorised them with PANTHER program into biological processes, being the metabolic pathways the most affected. We detected six groups of proteins with the STRING program involved in DNA topology, glycolysis, translation initiation, splicing, pentose pathway, and proteasome degradation. The main subexpressed protein network included mitochondrial proteins involved in oxidative phosphorylation. We propose BAG6, DDX39, ANXA8 and COX4 as putative biomarkers in breast cancer. BIOLOGICAL SIGNIFICANCE We report a set of differentially expressed proteins in the MCF7 and T47D (Luminal A), MDA-MB-231 (Claudin low) and SK-BR-3 (HER2(+)) breast cancer cell lines that have not been previously reported in breast cancer disease. From these proteins, we propose BAG6, DDX39, ANXA8 and COX4 as putative biomarkers in breast cancer. On the other hand, we propose sets of unique polypeptides in each breast cancer cell line that can be useful in the classification of different subtypes of breast cancer.

A case report of mucoepidermoid carcinoma of the parotid gland developing after radioiodine therapy for thyroid carcinoma

This is a report on a 19-year-old female who developed a low grade T2 N0 M0 mucoepidermoid carcinoma of the right parotid gland 3 years and 5 months after the post-operative treatment of 100 mCi of radioactive iodine (131I) for a papillary thyroid carcinoma. The parotid tumour appeared during the patients pregnancy. There are few reports of salivary gland cancer developing after radioiodine therapy for thyroid carcinoma and it is hoped that this report may stimulate others to investigate this association further in order to clarify the risk of secondary malignancies after radioiodine therapy.

RET Oncogene Mutations in Medullary Thyroid Carcinoma in Mexican Families

BACKGROUND Different RET oncogene mutations have been found to be associated with inherited medullary thyroid carcinoma (MTC) in the context of three different syndromes including multiple endocrine neoplasia types 2A (MEN 2A) and 2B (MEN 2B) and familial medullary thyroid carcinoma (FMTC). These mutations have been recorded in different populations, but to date there is no corresponding study in Mexican families. Our purpose was identification of RET mutations in Mexican families with inherited or sporadic MTC (SMTC) and search for RET protein expression as prognostic marker in MTC tumors. METHODS Nine unrelated families with MTC corresponding either to two MEN 2A, three MEN 2B, or four SMTC were studied. Screening of exons 10, 11, and 13-16 of RET oncogene in DNA from circulating lymphocytes and tumor samples were analyzed. Immuno- staining for RET was performed in the corresponding tumor. RESULTS Germline 918 ATG-->ACG RET mutation was present in three unrelated MEN 2B individuals and corresponding somatic mutation in one individual with SMTC; 634 TGC-->TTC RET mutation was detected in two related patients in an MEN 2A family and the 634 TGC-->TAC RET mutation was detected in 12 related individuals from a second MEN 2A family. RET protein expression was detected in all MTC tumors showing different staining intensity. CONCLUSIONS RET mutations found in Mexican patients with MTC are similar to those previously reported in several MTC families worldwide. This indicates that RET mutations are highly conserved and that MTC etiology does not depend to a great extent on environmental factors or ethnic differences. Detection of RET protein in MTC tissue sections is not useful as prognostic marker.

Quality control in planning and technique of radiotherapy with cobalt-60 for T1 glottic cancer increase local control and organ preservation

BACKGROUND In order to evaluate whether individualized technique and dosimetry of radiotherapy increase local control, organ preservation, and survival of patients with T1 glottic cancer, we reviewed 76 cases treated from 1979 to 1993. METHODS Group A included 32 patients treated from 1979 to 1989 with different techniques, based on clinical aspects. Group B included 44 patients treated from 1990 to 1993 with individualized technique according to tumor extension and patients anatomy. RESULTS Five-year local control with radiotherapy alone was achieved in 53% of group A versus 91% of group B (P > 0.005). Survival was similar in both groups with rescue surgery (90% versus 96%). Five-year survival with larynx preservation was 65% in group A versus 88% in group B (P = 0.02). Most recurrences (78%) appeared within 24 months of follow-up. CONCLUSION Adequate staging, individualized technique, computing planning using simulation and use of immobilization devices during cobalt-60 radiotherapy significantly increase local control and organ preservation in T1 glottic cancer.

Dual targeting of ANGPT1 and TGFBR2 genes by miR-204 controls angiogenesis in breast cancer

Deregulated expression of microRNAs has been associated with angiogenesis. Studying the miRNome of locally advanced breast tumors we unsuspectedly found a dramatically repression of miR-204, a small non-coding RNA with no previous involvement in tumor angiogenesis. Downregulation of miR-204 was confirmed in an independent cohort of patients and breast cancer cell lines. Gain-of-function analysis indicates that ectopic expression of miR-204 impairs cell proliferation, anchorage-independent growth, migration, invasion, and the formation of 3D capillary networks in vitro. Likewise, in vivo vascularization and angiogenesis were suppressed by miR-204 in a nu/nu mice model. Genome-wide profiling of MDA-MB-231 cells expressing miR-204 revealed changes in the expression of hundred cancer-related genes. Of these, we focused on the study of pro-angiogenic ANGPT1 and TGFβR2. Functional analysis using luciferase reporter and rescue assays confirmed that ANGPT1 and TGFβR2 are novel effectors downstream of miR-204. Accordingly, an inverse correlation between miR-204 and ANGPT1/TGFβR2 expression was found in breast tumors. Knockdown of TGFβR2, but not ANGPT1, impairs cell proliferation and migration whereas inhibition of both genes inhibits angiogenesis. Taken altogether, our findings reveal a novel role for miR-204/ANGPT1/TGFβR2 axis in tumor angiogenesis. We propose that therapeutic manipulation of miR-204 levels may represent a promising approach in breast cancer.

A SIMPLIFIED HISTOSCORE FOR THE ESTROGEN RECEPTOR ASSAY IN BREAST CANCER

Different histoscores combining the number of positive cells and the intensity of staining have been used to evaluate the estrogen receptor immunocytochemical assay (ER-ICA). Our aim was to investigate if the simple estimation of the amount of positive cells could be sufficient for the semiquantitative analysis of ER-ICA. Tissue from 51 women with ductal breast carcinoma was used. Half of each sample was processed with the quantitative assay (ER-EIA) and the other half with ER-ICA. Microscopical analysis was performed by two independent observers and classified on a simple scale from 0 to 4+. With EIA 31 cases (60.78%) were positive and 20 (39.21%) negative. With ER-ICA 29 (56.86%) had immunostaining, whereas 22 (43.13%) did not. 95.83% of the ER-ICA positive cases and 77.7% of ER-ICA negative had a good correlation with EIA values. Statistical analysis showed a high degree of correlation (r = 0.88 p 0.001). Hence, simple semiquantitative estimation in ER-ICA is sufficient to provide useful information for clinical use about ER content in tissue sections.