Mapping the tumor stress network reveals dynamic shifts in the stromal oxidative stress response.

The tumor microenvironment (TME) presents cells with challenges such as variable pH, hypoxia, and free radicals, triggering stress responses that affect cancer progression. In this study, we examine the stress response landscape in four carcinomas-breast, pancreas, ovary, and prostate-across five pathways: heat shock, oxidative stress, hypoxia, DNA damage, and unfolded protein stress. Using a combination of experimental and computational methods, we create an atlas of stress responses across various types of carcinomas.

p53 deficient breast cancer cells reprogram preadipocytes toward tumor-protective immunomodulatory cells.

The gene is mutated in approximately 30% of all breast cancer cases. Adipocytes and preadipocytes, which constitute a substantial fraction of the stroma of normal mammary tissue and breast tumors, undergo transcriptional, metabolic, and phenotypic reprogramming during breast cancer development and play an important role in tumor progression. We report here that p53 loss in breast cancer cells facilitates the reprogramming of preadipocytes, inducing them to acquire a unique transcriptional and metabolic program that combines impaired adipocytic differentiation with augmented cytokine expression.

The tumor microenvironment shows a hierarchy of cell-cell interactions dominated by fibroblasts.

The tumor microenvironment (TME) is comprised of non-malignant cells that interact with each other and with cancer cells, critically impacting cancer biology. The TME is complex, and understanding it requires simplifying approaches. Here we provide an experimental-mathematical approach to decompose the TME into small circuits of interacting cell types.

DNA methylation landscape of tumor-associated macrophages reveals pathways, transcription factors and prognostic value relevant to triple-negative breast cancer patients.

The accumulation of myeloid cells, particularly tumor-associated macrophages (TAMs), characterizes the tumor microenvironment (TME) of many solid cancers, including breast cancer. Compared to healthy tissue-resident macrophages, TAMs acquire distinct transcriptomes and tumor-promoting functions by largely unknown mechanisms. Here, we hypothesize the involvement of TME signaling and subsequent epigenetic reprogramming of TAMs.

Cancer-associated fibroblast compositions change with breast cancer progression linking the ratio of S100A4 and PDPN CAFs to clinical outcome.

Tumors are supported by cancer-associated fibroblasts (CAFs). CAFs are heterogeneous and carry out distinct cancer-associated functions. Understanding the full repertoire of CAFs and their dynamic changes as tumors evolve could improve the precision of cancer treatment.

MTCH2-mediated mitochondrial fusion drives exit from naïve pluripotency in embryonic stem cells.

The role of mitochondria dynamics and its molecular regulators remains largely unknown during naïve-to-primed pluripotent cell interconversion. Here we report that mitochondrial MTCH2 is a regulator of mitochondrial fusion, essential for the naïve-to-primed interconversion of murine embryonic stem cells (ESCs). During this interconversion, wild-type ESCs elongate their mitochondria and slightly alter their glutamine utilization.

Correlation between colposcopically directed biopsy and cervical loop excision.

Colposcopy is standard for diagnosis of cervical cancer precursors, but the development of diathermy loop electrodes for excision of the cervical transformation zone offers a technique for validation. Loop excision of the transformation zone was performed for 47 consecutive women with dysplasia in colposcopically directed biopsies using 20 x 8-mm electrodes. Specimens were marked for orientation and serially sectioned.

[Adequacy of of pacemakers responsive to the volume-minute ventilation rate in heart transplantation patients].

Purpose: To evaluate in the late post-operative period (PO) the chronotropic response to exercise of patients submitted to orthotopic cardiac transplantation (CT) and the implant of a cardiac pacemaker (PM).

Methods: A rate response ventricular PM (VVI+R) which uses minute ventilation (MV) as a sensor was implanted in five patients in the early PO of CT due to chronotropic incompetence. The patients were 31 to 64 years old and the indication to implant of PM was low ventricular escape rhythm following atrial taquicardia/bradycardia (one case) or sinus bradycardia (4 cases).

[Use of implantable pacemaker in the treatment of paroxysmal supraventricular tachycardia refractory to pharmacologic therapy].

Purpose: To evaluate the results with the use of an automatic antitachycardia pacemaker in patients with refractory paroxysmal supraventricular tachycardia.

Patients And Methods: Nine patients aged 32 to 63 years with symptoms from 2 to more than 40 years and prophylactic treatment with several antiarrhythmic drugs that had failed to control tachycardia. The frequency of attacks in the year before the implant was from 1 per month to 3 daily and 4 of patients required direct counter current cardioversion at least once.

An unusual receptor mediates adenosine-induced SA nodal bradycardia in dogs.

To characterize the receptor mediating the negative chronotropic effect of adenosine in dogs, experiments were performed on conscious dogs with chronically implanted cardiovascular instrumentation. Autonomic blockade was used to eliminate any reflex influences on heart rate. Intravenous bolus injections of various adenosine analogues caused dose-dependent, aminophylline-blockable reductions in heart rate with a potency order of 5'-(N-ethylcarboxyamido)-adenosine (NECA)-78:2-chloroadenosine-17:adenosine-1.