Current Opinion in Pharmacology最新文献

Hypogonadism is frequent with a prevalence of 2% in the general population. Hypogonadism may derive from any condition able to disrupt the hypothalamic-pituitary-testis (HPT) axis at one or more levels. Hypogonadism may be classified according to the age of onset, its potential reversibility and level of the HPT axis damage. The latter categorization is useful to decide on the treatment. Damages to the hypothalamus-pituitary may benefit from either GnRH, gonadotropin or T therapy with the former carrying the advantage of stimulating spermatogenesis. Conversely, when the testis is damaged, T therapy is the only option and restoration of spermatogenesis is not possible. Therefore, the choice of therapy is primarily based on the diagnosis and patients’ needs and both should be carefully considered.

Polycystic ovary syndrome is a prevalent endocrinopathy involving androgen excess, and anovulatory infertility. The disorder is also associated with many comorbidities such as obesity and hyperinsulinemia, and an increased risk of cardiovascular complications. Reproductive, endocrine, and metabolic symptoms are highly variable, with heterogenous phenotypes adding complexity to clinical management of symptoms. This review highlights recent findings regarding emerging therapies for treating polycystic ovary syndrome, including i) pharmacological agents to target androgen excess, ii) modulation of kisspeptin signalling to target central neuroendocrine dysregulation, and iii) novel insulin sensitisers to combat peripheral metabolic dysfunction.

Stomach cancer is an aggressive disease and represents a global health problem. The majority of patients with localised disease present with locally advanced cancer that requires multimodality treatment. Chemoradiotherapy delivered after D2 gastrectomy has been evaluated in a number of clinical studies and best evidence, thus far, does not support its use in the post-operative setting. Data from currently recruiting and ongoing trials with exploratory translational endpoints are eagerly awaited to direct the use of chemoradiotherapy in the neoadjuvant setting. Radiotherapy can be effective in the palliation of symptoms associated with advanced gastric cancer. Furthermore, Stereotactic Body Radiotherapy has the potential to provide long term disease control in a proportion of gastric cancer patients with oligometastatic liver disease.

Pancreatic ductal adenocarcinoma is an aggressive malignancy that carries a poor prognosis because the majority of patients present with locally advanced or metastatic disease. However, even patients who are fortunate enough to present with resectable disease are often plagued by high recurrence rates. While adjuvant chemotherapy has been shown to decrease the risk of recurrence after surgery, post operative complications and poor performance status after surgery prevent up to 50% of patients from receiving it. Given the benefits of neoadjuvant therapy in patients with borderline resectable disease, it is understandable that neoadjuvant therapy has been steadily increasing in patients with resectable cancers as well. In this review paper, we highlight the rational and existing evidence of using neoadjuvant therapy in all patients with resectable pancreatic adenocarcinoma.

Gonadotropin-releasing hormone (GnRH) is the final output of the central nervous system that drives fertility. A characteristic of GnRH secretion is its pulsatility, which is driven by a pulse generator. Each GnRH pulse triggers a luteinizing hormone (LH) pulse. However, the puzzle has been to reconcile the synchronicity of GnRH neurons with the scattered hypothalamic distribution of their cell bodies. A leap toward understanding GnRH pulses was the discovery of kisspeptin neurons near the distal processes of GnRH neurons, which secrete kisspeptins, potent excitatory neuropeptides on GnRH neurons, and equipped with dual, but opposite, self-modulatory neuropeptides, neurokinin B and dynorphin. Over the last decade, this cell-to-cell communication has been dissected in animal models. Today the 50-year quest for the basic mechanism of GnRH pulse generation may be over, but questions about its physiological tuning remain. Here is an overview of recent basic research that frames translational research.

For decades, chemoradiotherapy for early-stage disease and systemic chemotherapy for advanced disease have represented the mainstay of treatment for anal cancer. Over the last few years, however, the advent of immunotherapy has opened interesting therapeutic perspectives, with the establishment of new standards of care, and the development of clinical trials that may further shape the treatment algorithm for this tumour. In this review article, we discuss the rationale behind the use of immunotherapy for anal cancer and provide an overview of the available clinical data and ongoing efforts to build on these.

Individuals with chronic traumatic spinal cord injury (SCI) develop progressive multi-system health problems that result in clinical illness and disability. Systemic inflammation is associated with many of the common medical complications and acquired diseases that accompany chronic SCI, suggesting that it contributes to a number of comorbid pathological conditions. However, many of the mechanisms that promote persistent systemic inflammation and its consequences remain ill-defined. This review describes the significant biological factors that contribute to systemic inflammation, major organ systems affected, health risks, and the potential treatment strategies. We aim to highlight the need for a better understanding of inflammatory processes, and to establish appropriate strategies to address inflammation in SCI.

Recent advances in our understanding of host immune and cancer cells interactions have made immunotherapy a prominent choice in cancer treatment. Despite such promise, cell-based immunotherapies remain inapplicable to many patients due to severe limitations in the availability and quality of immune cells isolated from donors. Reprogramming technologies that facilitate the engineering of cell types of interest, are emerging as a putative solution to such challenges. Here we focus on the recent progress being made in reprogramming technologies with respect to the immune system and their potential for clinical applications.

Functional hypothalamic amenorrhea (FHA) is the most common cause of secondary amenorrhea in women of reproductive age. FHA is predominantly caused by stress, decreased caloric intake, excessive exercise, or a combination thereof. These physical, psychological, and metabolic stressors cause aberration in the pulsatile release of gonadotropin-releasing hormone (GnRH) and subsequently impair function of the hypothalamic–pituitary–ovarian (HPO) axis. Various neurotransmitters acting in the central nervous system are involved in control of the HPO axis and of these, kisspeptin is one of the most important. Corticotropin-releasing hormone (CRH), also inhibits the pulsatile secretion of GnRH and also acts as an intermediary between stress factors and the reproductive system. One of the main ongoing concerns in patients with FHA is chronic hypoestrogenism, a condition, which is associated with sexual dysfunction and infertility. It may also lead to osteoporosis, and predispose to neurodegenerative and cardiovascular diseases.

Treatment of FHA requires the elimination of causative factors, however, making the necessary lifestyle changes is not always easy to initiate and maintain. Broadening our knowledge of the complex neural mechanisms regulating reproductive function in which kisspeptin plays a key role can help in the development of new treatment options such as the potential of kisspeptin receptor agonists for patients with FHA.