Phenotypic Heterogeneity of Cancer Associated Fibroblasts in Cervical Cancer Progression: FAP as a Central Activation Marker.

Cervical cancer (CC) is the fourth leading cancer among women and is one of the principal gynecological malignancies. In the tumor microenvironment, cancer-associated fibroblasts (CAFs) play a crucial role during malignant progression, exhibiting a variety of heterogeneous phenotypes. CAFs express phenotypic markers like fibroblast activation protein (FAP), vimentin, S100A4, α-smooth muscle actin (αSMA), and functional markers such as MMP9. This study aimed to evaluate the protein expression of vimentin, S100A4, αSMA, FAP, and MMP9 in mesenchymal stem cells (MSC)-CAF cells, as well as in cervical cancer samples. MSC cells were stimulated with HeLa and SiHa tumor cell supernatants, followed by protein evaluation and cytokine profile to confirm differentiation towards a CAF phenotype. In addition, automated immunohistochemistry (IHQa) was performed to evaluate the expression of these proteins in CC samples at different stages. Our findings revealed a high expression of FAP in stimulated MSC cells, accompanied by the secretion of pro/anti-inflammatory cytokines. In the other hand, CC samples were observed to have high expression of FAP, vimentin, αSMA, and MMP9. Most importantly, there was a high expression of their activation proteins αSMA and FAP during the different stages. In the early stages, a myofibroblast-like phenotype (CAFs αSMA+ FAP+), and in the late stages a protumoral phenotype (CAF αSMA- FAP+). In summary, FAP has a crucial role in the activation of CAFs during cervical cancer progression.

Pleiotrophin and the Expression of Its Receptors during Development of the Human Cerebellar Cortex.

During embryonic and fetal development, the cerebellum undergoes several histological changes that require a specific microenvironment. Pleiotrophin (PTN) has been related to cerebral and cerebellar cortex ontogenesis in different species. PTN signaling includes PTPRZ1, ALK, and NRP-1 receptors, which are implicated in cell differentiation, migration, and proliferation. However, its involvement in human cerebellar development has not been described so far. Therefore, we investigated whether PTN and its receptors were expressed in the human cerebellar cortex during fetal and early neonatal development. The expression profile of PTN and its receptors was analyzed using an immunohistochemical method. PTN, PTPRZ1, and NRP-1 were expressed from week 17 to the postnatal stage, with variable expression among granule cell precursors, glial cells, and Purkinje cells. ALK was only expressed during week 31. These results suggest that, in the fetal and neonatal human cerebellum, PTN is involved in cell communication through granule cell precursors, Bergmann glia, and Purkinje cells via PTPRZ1, NRP-1, and ALK signaling. This communication could be involved in cell proliferation and cellular migration. Overall, the present study represents the first characterization of PTN, PTPRZ1, ALK, and NRP-1 expression in human tissues, suggesting their involvement in cerebellar cortex development.

Treatment of melasma with platelet-rich plasma: A self-controlled clinical trial.

Melasma is a common circumscribed hypermelanosis of sun-exposed areas of the skin. Platelet-Rich Plasma therapy has been evidenced to inhibit melanin synthesis in animals and humans. To determine the effectiveness of platelet-rich plasma as a treatment for melasma. Twenty female patient with melasma were involved in this study. The intervention included three Platelet-Rich Plasma application sessions at 15-day intervals. Patients were evaluated before and after treatment. Variables measured included the facial melanin concentration using the melasma area and severity index score, melasma quality of life scale satisfaction grade, and histologic changes. Mean age was 41 ± 7 years. An initial MELASQOL score of 42 ± 14.8 and final score of 16.6 ± 7.2 (p = 0.008) were reported; the initial and final MASI score were 15.5 ± 8.4 and 9.5 ± 7.2 (p = 0.001), respectively. The dermatoscopy examination revealed a decrease in pigmentation after intervention (p = 0.001). Histopathologic improvement was detected in reductions in cutaneous atrophy (14 [70%] vs. 11 [55%]), solar elastosis (15 [75%] vs.11 [55%]), and inflammatory infiltrate (9 [45%] vs. 6 [30%]), before and after treatment, respectively. The intervention was associated with decreased intensity of the melasma patch and improved skin quality, shown by the MELASQOL and MASI scores.

TYMS 2R3R polymorphism and DPYD [IVS]14+1G>A gene mutation in Mexican colorectal cancer patients.

OBJECTIVE: To examine the association between TYMS 2R3R polymorphism and DPYD [IVS]14+1G>A mutation by comparing healthy subjects with colorectal cancer (CRC) patients in the Mexican population. METHOD: Genotyping of the 2R/3R was performed by polymerase chain reaction (PCR) and [IVS]14+1G>A mutation by real-time PCR analysis. RESULTS: The observed frequencies of the TYMS 2R3R polymorphism and the -[IVS]14+1G>A mutation in DPYD did not indicate an increased risk for CRC (p>0.05). However we observed an association of the 2R/2R (OR 3.08, 95% CI 1.66-6.08, p=0.0017) and heterozygous (OR 1.98, 95% CI 1.32-2.97, p=0.0012) genotypes as risk factors when comparing controls and CRC patients that were also tobacco consumers. An association between the genotype and the disease was evident. The distribution of the 2R/2R genotype and hematological toxicity (adjusted OR 2.26, 95% CI 1.54-4.45, p=0.0259), heterozygous (2R/3R) with tumor stage III-IV (OR 1.81, 95% CI 1.11-2.94, p=0.020) and 2R/2R-2R/3R in non-chemotherapy response CRC patients with hematological (OR 2.3, 95% CI 1.21-4.4, p=0.014) and gastric toxicities (OR 3.11, 95% CI 1.18-8.2, p=0.035) confirmed that this factor may significantly contribute to the CRC susceptibility. CONCLUSION: TYMS 2R3R polymorphism and the -[IVS]14+1G>A mutation in DPYD was not associated with susceptibility to CRC. However, the 2R/2R and 2R/3R genotypes of TYMS polymorphism could significantly contribute to hematological and gastric toxicity in CRC patients in this sample population.

[Necrotizing scleritis and recurrent erythema nodosum: a diagnostic challenge]. / Escleritis necrotizante y eritema nodoso recurrente: un reto diagnóstico. Informe de un caso.

The necrotizing scleritis and recurrent erythema nodosum, two clinical entities difficult to diagnose and which represent a challenge to the physician. Tuberculosis produces both processes by an immune reaction of delayed hypersensitivity type IV to various antigenic components of mycobacteria. Most tuberculosis patients have no ocular history of pulmonary or systemic disease in up to 50 % and no evidence of pathology in the chest radiograph. An adequate treatment leads to a favorable prognosis. It occurs when the diagnosis of infection is made on time. We describe the case of a woman with necrotizing scleritis associated with recurrent erythema nodosum secondary to infection with Mycobacterium tuberculosis complex.

Human telomerase and alpha-methylacyl-coenzyme A racemase in prostatic carcinoma. A comparative immunohistochemical study.

Human telomerase detected by in situ hybridization has been demonstrated to be a useful tool for the diagnosis of malignancy and has also been tested by reverse transcriptase-polymerase chain reaction in several tumors such as hepatic cell carcinoma, melanoma, colonic carcinoma, gastric carcinoma, biliary carcinoma, breast carcinoma, mesothelioma, lung carcinoma, female tract carcinoma, and prostatic carcinoma. A monoclonal antibody (clone Tel-24) that allows for the detection of human telomerase reverse transcriptase (hTERT) in paraffin blocks of archival material has recently been developed. Carcinomas of cervix, endometrium, and breast have been studied by this method, but its value in prostatic carcinoma has not been explored; for that reason, we studied benign and malignant prostatic lesions by immunohistochemistry using paraffin embedded tissue. The aim of the study was to define the sensitivity and specificity of hTERT in prostate cancer, in comparison with alpha-methylacyl-coenzyme A racemase (AMACR) (P504-S). Fifty-five specimens of diverse prostatic lesions were selected for study (43 needle biopsies and 12 transurethral resections); there were 61 malignancies (47 infiltrating carcinomas and 14 high-grade prostatic intraepithelial neoplasias [PIN]) and 29 benign lesions (10 basal cell hyperplasias, 12 nodular hyperplasias, 4 chronic prostatitis, and 3 atrophic glands). Signal for hTERT nucleolar was detected in 31 of 47 infiltrating adenocarcinomas, in 11 of 14 PIN, and in none of 27 benign lesions (sensitivity, 71%; specificity, 100%). Diffuse cytoplasmic positivity for AMACR was found in 37 of 41 infiltrating adenocarcinomas, in 7 of 7 PIN, and in 6 of 22 benign lesions (sensitivity, 91%; specificity, 72%). These results indicate that hTERT is highly specific of malignancy, with no false-positive cases; however, it had lower sensitivity than AMACR.

[Vulvar metastatic disease: experience at the National Institute of Cancer of Mexico]. / Enfermedad metastásica vulvar: experiencia en el Instituto Nacional de Cancerología de México.

BACKGROUND: Malignant vulvar tumors account for less than 1% of the malignant lesions in women and between 3 to 5% of the malignant tumors from female genital tract. The most common malignant neoplasia is squamous cell carcinoma followed by melanoma and in last place sarcomas and metastasis. OBJECTIVE: To report the incidence and experience at the Instituto Nacional de Cancerologia of Mexico. MATERIAL AND METHODS: Vulvar metastasis were recorded from the files of pathology department of the Instituto Nacional de Cancerologia diagnosed from 1984 to 2002. Clinical and histological characteristics from these cases were evaluated as well as clinical behavior. RESULTS: Eight cases of vulvar metastasis were found from a total of 436 malignant vulvar neoplasias (1.8%). Primary tumor in six cases was located in genital area; in the other two the primary tumor was located in breast and bladder. Labium majus was the most frequent site of metastasis. All the patients died with disease progression in a period of one month to one year after the diagnosis of vulvar metastasis. CONCLUSION: Vulvar metastasis is a rare phenomenon; these lesions are in relation to advanced clinical stage and a poor prognosis.