Hematohidrosis, Hemolacria, and "Trichorrhage": A Systematic Review.

Introduction: Hematohidrosis and hemolacria are 2 conditions surrounded in religiousness, mysticism, and supernatural superstitions. While the mechanism is still unclear, these cases have amazed physicians for centuries. Methods: We performed a systematic review in PubMed from 2000 to mid-2021 accounting for 75 studies from which we included 60 cases in 53 articles which were described. Results: The median age of apparition was 24 years with the youngest case being 12 and the oldest 81. Some of the diseases were secondary to other causes such as hemangiomas and other neoplasias or epistaxis episodes. Most of the cases have been reported in India and the USA; most of them correspond to hemolacria alone (51.6%). Discussion: We have stated the basics of the substances involved in the coagulation process that have been described as genetically altered in some patients such as mucins, metalloproteinases, and fibrinogen, as well as propose a mechanism that can explain the signs of this particular entity and approach to its treatment as well as provide the first trichoscopy image of a patient with hemolacria.

miRNA signature associated with R-CHOP refractoriness in patients diagnosed with diffuse large B cell lymphoma.

Refractoriness remains as one of the challenges in patients with lymphoma under chemotherapy, and among biological regulators in cells driving this type of response are microRNAs (miRNAs). Different genes are constantly turned on or off according to the miRNAs expression profiles affecting the drug response in patients and their stability in serum and plasma makes them potential prognostic biomarkers in several diseases. Here we described a profile of miRNAs in plasma of diffuse large B cell lymphoma (DLBCL) patients. miRNA expression arrays were carried using pre-treatment plasma samples of sixteen patients, followed by a comparison between the responder and the non-responders. After six cycles of R-CHOP treatment, twelve out of sixteen patients were clinically diagnosed with complete response while in four patients no clinical response was observed. Between these groups, a signature of fifteen differential expressed miRNAs was found. The circulating miRNAs in plasma of patients with no response were related to the drug resistance in other types of cancer, by targeting genes involved in cell proliferation and apoptosis, among other cell processes.

3D Imaging Detection of HER2 Based in the Use of Novel Affibody-Quantum Dots Probes and Ratiometric Analysis.

Patients with breast cancer (BC) overexpressing HER2 (HER2+) are selected for Trastuzumab treatment, which blocks HER2 and improves cancer prognosis. However, HER2+ diagnosis, by the gold standard, immunohistochemistry, could lead to errors, associated to: a) variability in sample manipulation (thin 2D sections), b) use of subjective algorithms, and c) heterogeneity of HER2 expression within the tissue. Therefore, we explored HER2 3D detection by multiplexed imaging of Affibody-Quantum Dots conjugates (Aff-QD), ratiometric analysis (RMAFI) and thresholding, using BC multicellular tumor spheroids (BC-MTS) (~120 µm of diameter) as 3D model of BC. HER2+, HER2- and hybrid HER2+/- BC-MTS (mimicking heterogeneous tissue) were incubated simultaneously with two Aff-QD probes (anti-HER2 and negative control (NC), respectively, (1:1)). Confocal XY sections were recorded along the Z distance, and processed by automatized RMAFI (anti-HER2 Aff-QD/ NC). Quantifying the NC fluorescence allowed to predict the fraction of non-specific accumulation of the anti-HER2 probe within the thick sample, and resolve the specific HER2 level. HER2 was detected up to 30µm within intact BC-MTS, however, permeabilization improved detection up to 70µm. Specific HER2 signal was objectively quantified, and HER2 3D-density of 9.2, 48.3 and 30.8% were obtained in HER2-, HER2+ and hybrid HER2+/- permeabilized BC-MTS, respectively. Therefore, by combining the multiplexing capacity of Aff-QD probes and RMAFI, we overcame the challenge of non-specific probe accumulation in 3D samples with minimal processing, yielding a fast, specific spatial HER2 detection and objective quantification.

Understanding the HPV integration and its progression to cervical cancer.

Cervical cancer is one of the main causes of female cancer death worldwide, and human papilloma virus (HPV) its causal agent. To investigate viral oncogenesis several studies have focused on the effects of HPV oncoproteins E6 and E7 and the mechanisms by which these proteins stimulate the cellular transformation process. However, phenomena such as the physical state of the viral genome (episomal or integrated) and the effects of this integration on cell proliferation contribute new clues to understand how HPV infection causes carcinogenesis. New molecular technologies are currently facilitating these discoveries. This paper reviews the tumor development process initiated by HPV, recent findings on the process of viral integration into the host genome, new methods to detect HPV integration, and derived associated effects.

BRAF Mutation (V600E) Prevalence in Mexican Patients Diagnosed with Melanoma.

BACKGROUND: B-Raf is a serine/threonine protein kinase activating the MAP kinase/ERK-signaling pathway. It has been shown that 50% of melanomas harbor activating BRAF mutations, with over 90% being the V600E mutation. OBJECTIVE: The goal of this research was to determine the prevalence of the BRAF V600E mutation in patients from Central Mexico diagnosed with primary melanoma. METHODS: Skin biopsies from 47 patients with melanoma were obtained from the dermatology department of the Hospital General 'Dr. Manuel Gea González' in Mexico City. For BRAF mutation determination, after DNA isolation, the gene region where the mutation occurs was amplified by PCR. Subsequently, the presence or absence of the V600E mutation was detected by Sanger sequencing performed at the private molecular diagnostic laboratory Vitagénesis in Monterrey, Mexico. RESULTS: Of the 47 patients sampled, 6.4% harbored the V600E mutation. No statistical significance was found between mutations and the type of tumor.

Cancer cell specific cytotoxic effect of Rhoeo discolor extracts and solvent fractions.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional or folk medicine has led to the discovery of important bioactive substances used in several health-related areas. Phytochemicals in Rhoeo discolor (R. discolor) extracts have proven to have important cancer cell specific cytotoxic activity. In the present research, we determined the cytotoxic effect of extracts of R. discolor, a plant commonly used in Mexico for both medicinal and ornamental purposes. AIM OF THE STUDY: We evaluated the cytotoxic effects against three representative human cancer cell lines: HT-29 colon cancer, Hep-G2 liver cancer and PC-3 prostate cancer cell lines, as well as a control fibroblast cell line NIH 3T3. MATERIALS AND METHODS: Ten different crude extracts were tested along with fractions derived from the five most bioactive crude extracts. Analytical data, HPLC-MS-TOF, revealed a high content of phenolic compounds such as anthocyanins, ferulic, vanillic, chlorogenic and p-coumaric acid in the extracts. Phenolic compounds have previously been reported as health beneficial with antioxidant and potential cancer specific cytotoxic effects. RESULTS: Studies revealed that low concentrations of these crude bioactive extracts (10µg/ml) and their fractions (50µg/ml) were effective as cancer specific cytotoxic agents, since they caused a significant proliferation inhibition on cancer cell lines (up to 94.2% in HT-29, 92.9% in Hep-G2 and 61.8% in PC-3 of apoptosis induction) with little harm to the control cell line (no higher than 28.3% apoptosis induction), and, importantly, the most effective extracts were mainly water, methanol and ethanol based. CONCLUSIONS: These results suggest that a diet containing these compounds may function as a medical aid or chemoprotective.

Technological Evolution in the Development of Therapeutic Antibodies.

Immunotherapy is defined as the use of the immune system or components of it, such as key immune molecules, to fight diseases or invading infectious agents. Modern biotechnology provides industrial versions of immune molecules (components of the immune system) naturally produced by the human body. Immune molecules such as monoclonal antibodies are used as therapeutics in several disease conditions. In recent years a new group of antibody based molecules has been developed to replace monoclonal antibodies, given their ability to overcome some of the limitations of the latter. The first clinical trials with these new molecules have been very encouraging and the promise is that they will be released to the market very soon. This in turn has stimulated more research on new versions of antibody based therapeutics by biotechnological companies supported by the pharmaceutical industry and in many cases in collaboration with academic institutions.