Phosphoproteomic analysis of neoadjuvant breast cancer suggests that increased sensitivity to paclitaxel is driven by CDK4 and filamin A.

Precision oncology research is challenging outside the contexts of oncogenic addiction and/or targeted therapies. We previously showed that phosphoproteomics is a powerful approach to reveal patient subsets of interest characterized by the activity of a few kinases where the underlying genomics is complex. Here, we conduct a phosphoproteomic screening of samples from HER2-negative female breast cancer receiving neoadjuvant paclitaxel (N = 130), aiming to find candidate biomarkers of paclitaxel sensitivity. Filtering 11 candidate biomarkers through 2 independent patient sets (N = 218) allowed the identification of a subgroup of patients characterized by high levels of CDK4 and filamin-A who had a 90% chance of achieving a pCR in response to paclitaxel. Mechanistically, CDK4 regulates filamin-A transcription, which in turn forms a complex with tubulin and CLIP-170, which elicits increased binding of paclitaxel to microtubules, microtubule acetylation and stabilization, and mitotic catastrophe. Thus, phosphoproteomics allows the identification of explainable factors for predicting response to paclitaxel.

[Ultrastructural aspects of lesions caused by Mycobacterium spp in AIDS]. / Aspectos ultraestructurales de las lesiones producidas por Mycobacterium spp en el SIDA.

Samples from necrotizing lesions in eight autopsy cases of AIDS were examined with transmission electron microscopy. They were selected among 35 autopsies of Mycobacterium spp infection and AIDS, and were part of a series of 230 autopsy cases of AIDS performed from 1984 to 1995 in the Anatomopathologic Institute at Central University of Venezuela. Ultrastructural aspects of micobacteriae, their relationship with macrophages and tissue alterations are discussed and related to the immune defcit observed in AIDS patients.

[An ultrastructural evaluation of Pneumocystis carinii]. / Evaluación ultraestructural del Pneumocystis carinii.

The pneumocystis carinii (PNC) is a challenge, because its taxonomy has not been completely explained. PNC seems to be a chimera with fungal and parasitic characteristics. The objective of the present study is to analyze the different stages observed in PNC using transmission electron microscopy in order to correlate them with bibliographic reports regarding a possible taxonomic classification. The trophic stage was the form most frequently encountered in alveolar spaces and their organisms varying in size and shape from 6 to 20 microns. Cyst were round or oval, with diameters ranging between 4 and 12 microns, showing four intracystic bodies were individually limited by a membrane. Connections between the membrane of intracystic bodies and junctions between them and the inner cell membrane of the cyst wall were also observed. Our ultrastructural findings appear to be in agreement with several reports which considered PNC among the fungi, most likely related them to the non-gemating Ascomycetes.

Paracoccidioidomicosis del cuello uterino: presentación de un caso / Paracoccidioidomycosis of uterine cervix: reported a case

Se presenta un caso de paracoccidioidomicosis de cuelo uterino; el primer caso descrito en nuestro medio, tal vez el segundo caso publicado a nivel mundial. Se hacen comentarios desde el punto de vista clínico, de microscopia de luz y de microscopia electrónica de transmisión

[Importance of transmission electron microscopy in the diagnosis of a Venezuelan equine encephalitis outbreak in 1995 in the Venezuelan Guajira]. / Importancia de la microscopía electrónica de transmisión en el diagnóstico de la epidemia de encefalitis equina venezolana de 1995 en la Guajira Venezolana.

Transmission electron microscopy of the brain in 25 newborn mice was performed. Mice were intracerebrally inoculated with cultured VERO cells infected with VEE to be used as positive control, with samples of serum of cerebrospinal fluid from patients with clinical symptoms and signs of encephalitis, with serum from healthy patients or with serum from sick equines. Borate bovine albumin serum was also inoculated in some mice to be used as negative control. All samples were obtained during the epizootic and epidemic outbreak in the Venezuelan Guajira area, northern of Zulia State during October 1995. The ultrastructural study was blindly performed, however the presence of Togavirus particles were detected in 100% of the virologically positive cases. The usefulness, accuracy and speed of the employed methodology is stressed.

[Pulmonary alveolar proteinosis: ultrastructural study of 4 cases]. / Proteinosis alveolar pulmonar: estudio ultraestructural de cuatro casos.

Pulmonary Alveolar Proteinosis (PAP) is a rare and diffuse lung disease characterized by the abnormal deposition of PAS positive, lipoproteinaceous material in the alveolar spaces. It has been related, mainly, to alterations in the immune state and to secondary infections. We studied four cases of PAP diagnosed by light microscopy. In two cases we were able to demonstrate disseminated Histoplasmosis related to immunodeficiency states (AIDS and malnutrition), one case with Pneumocystis carinii infection and AIDS, and one case with no related pathology. Granular and electron dense material, concentric myelin figures, and variable-sized osmiophilic bodies were observed by electron microscopy. We found yeast-like structures, trophozoites and cysts in the alveolar spaces, in the Histoplasmosis and Pneumocystic carinii infection cases, respectively. In one of our cases, the circulating neutrophils showed crystalloid inclusions in the nucleus. PAP should be considered in the differential diagnoses of patients with pulmonary infiltrates.

[Application of electron microscopy and immunohistochemistry to the study of malignant tumors: a review of their diagnostic importance]. / Aplicación de la microscopía electrónica y de la inmunohistoquímica a1 estudio de los tumores malignos: una revisión de su importancia diagnóstica.

The results of examining in the course of the past twenty years a considerable number of malignant tumors with transmission electron microscopy and immunohistochemistry are discussed. The neoplasms were divided into epithelial tumors, tumors of fusiform cells, malignant round cell tumors and tumors of endocrine nature. The main ultrastructural findings and the results of immunohistochemical studies were pointed out regarding their contributory role in the diagnosis as well as for the prognosis and treatment of patients with cancer.

[Histopathology and ultrastructure of chromomycosis caused by Cladosporium carrionii]. / Histopatología y ultraestructura de la cromomicosis causada por Cladosporium carrionii.

Light and electron microscopic study of chromomycosis caused by C. carrionii was undertaken. Biopsies from 10 patients were taken and processed by means of conventional histopathologic techniques of hematoxylin and eosine and by transmission electron microscopy. Granulomatous and suppurative components of the infection process were observed by the histological procedure, other cellular elements such as lymphocytes, plasma cells, eosinophils and Langerhans cells were present. The fungus was observed free or within phagocyticcells. Ultrastructural evidence revealed that it was surrounded by a wide multilayered and electron dense cell wall. Its cytoplasmic membrane presented invaginations and vacuoles containing the electron-dense material. We suggest the existence of a secretion-excretion process of a melanin-like dark pigment, which is accumulated on the cell wall of fungus, increasing the resistance of fungal cell to its destruction by phagocytic cell. It is necessary to determine the exact role of Langerhans cells in chromomycosis caused by C. carrionii.