A non-catalytic function of carbonic anhydrase IX contributes to the glycolytic phenotype and pH regulation in human breast cancer cells.

The most aggressive and invasive tumor cells often reside in hypoxic microenvironments and rely heavily on rapid anaerobic glycolysis for energy production. This switch from oxidative phosphorylation to glycolysis, along with up-regulation of the glucose transport system, significantly increases the release of lactic acid from cells into the tumor microenvironment. Excess lactate and proton excretion exacerbate extracellular acidification to which cancer cells, but not normal cells, adapt. We have hypothesized that carbonic anhydrases (CAs) play a role in stabilizing both intracellular and extracellular pH to favor cancer progression and metastasis. Here, we show that proton efflux (acidification) using the glycolytic rate assay is dependent on both extracellular pH (pHe) and CA IX expression. Yet, isoform-selective sulfonamide-based inhibitors of CA IX did not alter proton flux, which suggests that the catalytic activity of CA IX is not necessary for this regulation. Other investigators have suggested the CA IX co-operates with the MCT transport family to excrete protons. To test this possibility, we examined the expression patterns of selected ion transporters and show that members of this family are differentially expressed within the molecular subtypes of breast cancer. The most aggressive form of breast cancer, triple-negative breast cancer, appears to co-ordinately express the monocarboxylate transporter 4 (MCT4) and carbonic anhydrase IX (CA IX). This supports a possible mechanism that utilizes the intramolecular H+ shuttle system in CA IX to facilitate proton efflux through MCT4.

The Benefits of Osteopathic Manipulative Treatment on a Patient With Ehlers-Danlos Syndrome.

Ehlers-Danlos syndrome (EDS) is a disorder affecting connective tissue throughout the body. Inherited through several different genetic mutations, the EDS symptoms of hyperextensibility, hypermobility, and fragility cause significant somatic and visceral issues in those affected. Chronic somatic dysfunction, pain, and systemic involvement create lifelong comorbidities and discomfort for these patients. One in every 5,000 individuals is burdened with EDS worldwide; in the US, the range has been reported to be 1/2,500-1/5,000 people. Very few patients with EDS in the literature have been documented and treated with osteopathic manipulative treatment (OMT). The objective of this case report is to describe the response of an EDS patient to outpatient OMT over a series of three office visits. The patient has verbally consented to OMT at each encounter. A combination of soft tissue manipulation, muscle energy, Still's technique, counterstrain, and high-velocity low-amplitude (HVLA) was performed in the head and neck, thoracic, lumbar, ribs, and lower extremity regions. During the three clinic visits of this patient, OMT was performed in the same regions by the student physician under the supervision of the attending physician. At each visit, the patient was asked to report their pain levels pre- and post-treatment and assess symptom improvement using a one to 10 pain scale, as well as any subjective symptoms they are experiencing. Following each treatment, as well as at each follow-up encounter, the patient reported marked pain and symptom improvement. The objective of this case report is to describe the benefits that one patient experienced from three clinic visits. These results showed that subjective improvement in respiratory, gastrointestinal, and musculoskeletal symptoms secondary to the longstanding history of EDS may be possible through the use of OMT.