B7-H3 Associates with IMPDH2 and Regulates Cancer Cell Survival.

Lung cancer is one of the most common cancers worldwide, and despite improvements in treatment regimens, patient prognosis remains poor. Lung adenocarcinomas develop from the lung epithelia and understanding how specific genetic and environmental factors lead to oncogenic transformation in these cells is of great importance to define the pathways that contribute to tumorigenesis. The recent rise in the use of immunotherapy to treat different cancers has prompted the exploration of immune modulators in tumour cells that may provide new targets to manipulate this process. Of these, the B7 family of cell surface receptors, which includes PD-1, is of particular interest due to its role in modulating immune cell responses within the tumour microenvironment. B7-H3 (CD276) is one family member that is upregulated in many cancer types and suggested to contribute to tumour-immune interactions. However, the function and ligand(s) for this receptor in normal lung epithelia and the mechanisms through which the overexpression of B7-H3 regulate cancer progression in the absence of immune cell interactions remain unclear. Here, we present evidence that B7-H3 is associated with one of the key rate-limiting metabolic enzymes IMPDH2, and the localisation of this complex is altered in human lung cancer cells that express high levels of B7-H3. Mechanistically, the IMPDH2:B7-H3 complex provides a protective role in cancer cells to escape oxidative stress triggered by chemotherapy, thus leading to cell survival. We further demonstrate that the loss of B7-H3 in cancer cells has no effect on growth or migration in 2D but promotes the expansion of 3D spheroids in an IMPDH2-dependent manner. These findings provide new insights into the B7-H3 function in the metabolic homeostasis of normal and transformed lung cancer cells, and whilst this molecule remains an interesting target for immunotherapy, these findings caution against the use of anti-B7-H3 therapies in certain clinical settings.

A Rare Occurrence of Phantom Tongue Pain.

This is a case of phantom tongue pain observed in a 65-year-old male with a history of adenoid cystic carcinoma with involvement of the base of the tongue and supraglottic laryngopharyngeal cancer who underwent a laryngopharyngectomy and glossectomy for treatment. The patient subsequently developed phantom tongue pain in acute rehabilitation. Post total glossectomy phantom pain is rare, and as this is a singular appendage, current techniques that rely on the presence of an intact limb, such as mirror therapy could not be applied to our patient. Therefore mental imagery techniques originally developed for extremity amputation required adaptation to the context of total glossectomy. Recommended anticonvulsant medications, desensitization, and mental imagery techniques for phantom limb pain were effective in relieving the patient's phantom tongue pain. Utilizing therapeutic desensitization techniques may allow for the direction of neuroplasticity in order to decrease pain.

Psychogenic Polydipsia in a Patient With a Clinical Triad.

Psychogenic Polydipsia (PP) is a condition involving excessive fluid intake causing hyponatremia. While the mechanism is unknown, treating arginine vasopressin (AVP) dysregulation with the class of drugs, vaptans, during acute psychotic episodes has been an effective treatment. These patients may present with a triad of acute psychosis, polydipsia, and electrolyte imbalances suggesting a syndrome of inappropriate antidiuretic hormone. Our patient is a 57-year-old female with a past medical history of schizophrenia who presented with seizures due to severe hyponatremia in the context of excessive water consumption and mild delusions regarding her sister. Her episodes of neural dysfunction started after she stopped taking her antipsychotic medications, making a drug-induced syndrome of inappropriate antidiuretic hormone secretion (SIADH) less likely. However, she had a normal urine osmolality raising suspicion of antidiuretic hormone involvement. The mechanism of hyponatremia in the context of polydipsic schizophrenia is not well established. Some evidence suggests that brain changes may cause AVP dysregulation, which can be exacerbated by acute psychotic episodes. Our case report describes a clinical scenario with the clinical triad of acute psychosis, polydipsia, and electrolyte imbalances suggestive of this mechanism.