1,722,510 research outputs found
Clinical pharmacology of progestins
No full textINTRODUCTION: In this paper, we report general pharmacological profile and major biological activities of natural progesterone (P) and progestins. The aim of this article consists of synthesizing the principal aspects of pharmacology and metabolism of P and progestins related to the clinical consequences of their use.EVIDENCE ACQUISITION: We review scientific literature on the topic "progestins, " evaluating the most relevant data from original articles, reviews, and meta-analyses.EVIDENCE SYNTHESIS: Progestins represent a specific class of synthetic analogues of P clinically employed (alone or associated with estrogens) to manage several gynecological conditions, for instance multiple abortions, luteal phase defect, premenstrual syndrome, abnormal uterine bleeding, endometriosis, and menopause (for hormone replacement therapy). Besides their use in the field of contraception, many non-contraceptive benefits of estroprogestins are mostly due to the activities of progestins. Pharmacological characteristics, dosage and individual metabolism could be listed among the principal aspects influencing their clinical effects.CONCLUSIONS: The choice of each progestin according to its pharmacological profile is crucial for the appropriate management of any gynecological condition. An aware knowledge of these compounds is fundamental to hone medical practice
Osteoporosis and cardiovascular disease: an update
No full textOsteoporosis (OP) and cardiovascular diseases (CVD) are the most important causes of mortality and morbility in the elderly. Lots of studies showed a correlation between bone loss and cardiovascular risk mediated by the vascular calcification. The relationship between OP and CVD could be firstly explained by their common risk factors such as age, smoking, alcohol consumption, physical activity and menopause. However, other different hypotheses were proposed to clarify this link. Multiple factors, for example bone morphogenetic proteins, osteoprotegerin, receptor activator of nuclear factor κB ligand, parathyroid hormone, phosphate, oxidized lipids and vitamins D and K seemed to be involved in both conditions, indicating a possible common pathophysiologic mechanism. We review and discuss the available data describing this association. Further studies are necessary to better investigate similarities between OP and CVD
Does ST analysis of fetal ECG reduce cesarean section rate for fetal distress?
No full textObjective: Each pregravidic, gestational or intrapartum complication may, per se, have a different impact on the operative delivery rate, regardless of which fetal monitoring system was adopted. We wanted to verify if CTG plus ST interval analysis (STAN) of fetal ECG might be able to reduce the number of operative delivery for fetal distress in high-risk pregnancies compared to low-risk women monitored with CTG alone. Materials and methods: In this cohort study, we evaluated 100 high-risk pregnancies consecutively with STAN® S31 (Neoventa Medical, Gotenburg, Sweden) and 160 low-risk pregnancies consecutively with continuous CTG (Hewlett Packard, 50 IP, Palo Alto, CA). Results: We found that STAN monitoring, although associated with a higher total operativity rate, both vaginal (11% versus 3.12%, p = 0.015) and cesarean (17% versus 4.37%, p = 0.001), reduced the cesarean section rate performed for fetal distress (29.41% versus 85.71%, p = 0.023) compared with low-risk CTG monitoring group. Conclusion: CTG plus ST interval analysis of fetal ECG reduced the risk of operative cesarean delivery for fetal distress in high-risk gestations
An update on the pharmacotherapy for endometrial cancer
No full textAbstract
INTRODUCTION: Endometrial cancer (EC) is the seventh most common malignancy in women. Most cases have a favorable prognosis because they present an early stage disease at diagnosis. Treatment currently comprises surgery with or without adjuvant approaches. A combination of radiation therapy, chemotherapy or hormonal therapy (HT) is usually administered. This article gives an update concerning the role of synthetic drugs in EC, reviewing the most recent data from Phase III randomized-controlled trials onwards.
AREAS COVERED: Over the years, chemotherapy has become the treatment mainstay in both high-risk or locally advanced EC and in metastatic or recurrent disease. Carboplatin plus paclitaxel is currently considered the standard chemotherapy regimen with a well-tolerated toxicity profile. HT is an alternative option in women with advanced EC and important co-morbidities, and in young women with very early stage disease.
EXPERT OPINION: Basic results of EC treatment during the last decade were collected. There is a need of more advances in treatment. The use of biomarkers, necessary for the success of a therapeutic strategy, and the identification of an ad-hoc population, are two important goals. In the authors' opinion, the development of comprehensive tumor bio-banks and international networks represent the right approach to foster translational studies and obtain improvement in patient outcomes
ASO Author Reflections: Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) for Platinum-Resistance Ovarian Cancer Patients
No full textPIPAC-OV3: A multicenter, open-label, randomized, two-arm phase III trial of the effect on progression-free survival of cisplatin and doxorubicin as Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) vs. chemotherapy alone in patients with platinum-resistant recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer
No full textAbstract
BACKGROUND:
Recurrent, platin-resistant ovarian cancer (rPROC) has a poor survival. Even with the AURELIA trial, which is the best available treatment today, progression-free survival (PFS) is still only 6.7 months from the start of the second-line chemotherapy. Innovative, effective therapies are urgently needed. Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) is a novel drug delivery system for administering drugs into the abdomen. PIPAC with cisplatin and doxorubicin (PIPAC C/D) may be safely used at an intraperitoneal dose of 10.5 mg/m2 and 2.1 mg/m2, respectively. Systemic toxicity of this therapy is low. In a phase II trial with 53 women, 62 % patients had an objective tumor response. Tumor regression on histology was observed in 76 % patients who underwent all three PIPACs. Randomized phase III studies are now required to evaluate the effect of PIPAC C/D compared to other standard treatments (sequential or simultaneous applications with systemic chemotherapy).
METHODS:
The present phase III study is a prospective, open, randomized, multicentric pivotal trial. A total of 244 patients will be randomly assigned (1:1) to the control (A) or to the experimental (B) group. Group A: Systemic palliative chemotherapy, physician's best choice (monotherapy consisting of pegylated liposomal doxorubicin or topotecan or gemcitabine or paclitaxel weekly. Bevacizumab can be used in combination with paclitaxel, topotecan, or pegylated liposomal doxorubicin). Group B: Intraperitoneal chemotherapy, 3×PIPAC C/D, performed every 6 weeks. Combination with systemic therapy is not allowed. Treatment is continued until disease progression, death, or patient refusal. In case of progression, no recommendation for further therapy is given by protocol. Patients are allowed to receive PIPAC C/D or systemic chemotherapy after study termination. The primary endpoint is PFS (according to RECIST v1.1) or death from any cause. The co-primary endpoint is the health-related quality of life (HRQoL) measured as the global health status (GHS, QLQ-30 of EORTC). Secondary outcomes comprise overall survival, safety (CTCAE 5.0), and tumor response according to peritoneal regression grading score (PRGS).
DISCUSSION:
We expect PIPAC C/D to control peritoneal disease and preserve the QoL on this subset of patients.
TRIAL REGISTRATION:
The EudraCT number 2018-003664-31.
KEYWORDS:
Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC); chemotherapy; platin-resistant ovarian cancer (rPROC); randomized phase III tria
Main implications related to the switch to BRCA1/2 tumor testing in ovarian cancer patients: a proposal of a consensus
No full textSince the approval of the first poly (adenosine diphosphate [ADP]) ribose polymerase inhibitor (PARPi; olaparib [LynparzaTM]) for platinum-sensitive relapsed high grade ovarian cancer, with either germline or somatic BRCA1/2 deleterious variants, the strategies for BRCA1/2 are dynamically changing. Along with germline testing within the context of familial or sporadic ovarian cancer, patients are now being referred for BRCA1/2 genetic assay above all for treatment decisions: in this setting tumour BRCA assay can allow to identify an estimated 3-9% of patients with peculiar somatic BRCA1/2 mutations. These women could also benefit from PARPi therapy. This new type of approach is really challenging, in particular due to the technical and analytical difficulties regarding low quality DNA deriving from formalin-fixed, paraffin-embedded (FFPE) specimens.
Aim: in this manuscript, we try to a) underline many issues related to BRCA1/2 analysis by next generation sequencing technologies (NGS), b) provide some responses to many questions regarding this new paradigm related to OvCa patients' management. Some considerations for incorporating genetic analysis of ovarian tumour samples into the patient pathway and ethical requirements are also provided.
Methods: we used our retrospective data based on thousands of ovarian cancer women sequenced for BRCA1/2 genes.
Discussion: tumor BRCA1/2 assay should be rapidly introduced in routine laboratory practice as first line testing by using harmonized pipelines based on consensus guidelines
ASO Author Reflections: Image-Guided Intraoperative Tissue Assessment for Guidance in Oncologic Surgery: From Frozen Section to Digital Surgery
No full textN
beta III-Tubulin: biomarker of taxane resistance or drug target?
No full textINTRODUCTION: βIII-Tubulin (TUBB3) is predominantly expressed in neurons of the central and peripheral nervous systems, while in normal non-neoplastic tissues it is barely detectable. By contrast, this cytoskeletal protein is abundant in a wide range of tumors. βIII-Tubulin is linked to dynamic instability of microtubules (MTs), weakening the effects of agents interfering with MT polymerization. Based on this principle, early studies introduced the classical theory linking βIII-tubulin with a mechanism of counteracting taxane activity and accordingly, prompted its investigation as a predictive biomarker of taxane resistance.
AREAS COVERED: We reviewed 59 translational studies, including cohorts from lung, ovarian, breast, gastric, colorectal and various miscellaneous cancers subject to different chemotherapy regimens.
EXPERT OPINION: βIII-Tubulin functions more as a prognostic factor than as a predictor of response to chemotherapy. We believe this view can be explained by βIII-tubulin's association with prosurvival pathways in the early steps of the metastatic process. Its prognostic response increases if combined with additional biomarkers that regulate its expression, since βIII-tubulin can be expressed in conditions, such as estrogen exposure, unrelated to survival mechanisms and without any predictive activity. Additional avenues for therapeutic intervention could emerge if drugs are designed to directly target βIII-tubulin and its mechanism of regulation
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