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Prediction of cancer drugs by chemical-chemical interactions.

Cancer, which is a leading cause of death worldwide, places a big burden on health-care system. In this study, an order-prediction model was built to predict a series of cancer drug indications based on chemical-chemical interactions. According to the confidence scores of their interactions, the order from the most likely cancer to the least one was obtained for each query drug. The 1(st) order prediction accuracy of the training dataset was 55.93%, evaluated by Jackknife test, while it was 55.56% and 59.09% on a validation test dataset and an independent test dataset, respectively. The propos

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… Mitotane-Cancers of the urinary system and male genital organs Mitotane ( D00420 ) is the first-line drug for metastatic adrenocortical carcinoma [45] , [46] , [47] , and also used for the adjuvant therapy after removing the primary tumor [48] . … Prolonged regression with mitotane therapy. JAMA 246: 1706–1707. 48. Terzolo M, Angeli A, Fassnacht M, Daffara F, Tauchmanova L, et al. (2007) Adjuvant mitotane treatment for adrenocortical carcinoma. N Engl J Med 356: 2372–2380. 49. …

Cushing's syndrome.

Cushing's syndrome remains one of the most challenging problems in clinical endocrinology. Cushing's disease is caused in the majority of cases by basophil pituitary microadenomas which may be successfully treated by trans-sphenoidal hypophysectomy. Treatment with metyrapone or o,p'-DDD can always induce a clinical remission but not a cure, and neurotransmitter therapy may be effective in a minority of cases. Pituitary irradiation cures about half of cases in the long-term and may be used for surgical failures. Tumours producing ectopic ACTH are frequently benign, small and occult and may prod

Arrhythmias, conduction disorders and sudden cardiac death in cancer patients and survivors: expert opinion of the working groups on cardio-oncology and on electrophysiology of the hellenic cardiac society.

Advances in cancer therapeutics have significantly improved patient survival; however, cardiotoxic effects-including arrhythmias-have emerged as a growing clinical concern. This expert opinion, developed by the Working Groups on Cardio-Oncology and Electrophysiology of the Hellenic Cardiological Society, aims to raise awareness of the increasing burden of arrhythmias in cancer patients and survivors. This document explores the multifactorial etiology of arrhythmias in this population, including patient-related factors, the direct effects of malignancy, and the arrhythmogenic potential of thera

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… and CYP2D6 | Alternative antiarrhythmic agent or regular monitoring for signs of toxicity such as bradycardia, QTc prolongation, PR or QRS widening Amiodarone | AKL TKI (brigatinib, ceritinib crizontinib, lorlatinib) Alkylating agent (ifosfamide) Antiandrogen (enzalutamide, abiraterone, apalutamide, mitotane … of plasma levels and signs of toxicity Diltiazem Verapamil | AKL TKI (brigatinib, ceritinib crizontinib, lorlatinib) Alkaloid (irinotecan, topotecan) ANT (daunorubicin, doxorubicin etoposide) Anthracycline (doxorubicin) Anti-HER2 TKI (tucatinib) Antiandrogen (abiraterone, apalutamide, enzalutamide, mitotane …

Drug Repurposing Approaches towards Defeating Multidrug-Resistant Gram-Negative Pathogens: Novel Polymyxin/Non-Antibiotic Combinations.

Multidrug-resistant (MDR) Gram-negative pathogens remain an unmet public health threat. In recent times, increased rates of resistance have been reported not only to commonly used antibiotics, but also to the last-resort antibiotics, such as polymyxins. More worryingly, despite the current trends in resistance, there is a lack of new antibiotics in the drug-discovery pipeline. Hence, it is imperative that new strategies are developed to preserve the clinical efficacy of the current antibiotics, particularly the last-line agents. Combining conventional antibiotics such as polymyxins with non-an

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… Mitotane, an antineoplastic drug used for the treatment of adrenal cancers [ 98 ], displayed synergy with polymyxin B against polymyxin-resistant MDR A. baumannii , P. aeruginosa , and K. pneumoniae in vitro. … The in vitro synergy was further confirmed in a mouse burn wound model, in which the combination treatment decreased wound infection by a polymyxin-resistant A. baumannii isolate, compared to either polymyxin B or mitotane monotherapy. …

Diagnosis and treatment of pituitary adenomas.

Pituitary tumors cause symptoms by secreting hormones (prolactin, PRL, responsible for amenorrhea-galactorrhea in women and decreased libido … tory after surgery. In waiting for the effects of radiotherapy, adrenal steroidogenesis inhibitors (mitotane, ketoconazole) may be indicated. If drugs are not available or not tolerated, bilateral adrenalectomy may be proposed. For patients with clinically non functioning adenomas (generally gonadotropin-secreting adenomas on immunocytochemistry), trans-sp …

Adrenocortical Carcinoma: A Challenging Diagnosis.

Adrenocortical carcinoma (ACC) is a rare malignancy with aggressive behaviour and a poor prognosis. Patients can present with adrenal hormonal excess or with nonspecific symptoms driven by the presence of an abdominal mass or metastatic disease. Many are completely asymptomatic and diagnosed incidentally. ACC can cause considerable morbidity and mortality, mostly due to its ability to invade surrounding tissues, produce hormones, and spread to distant organs. The authors describe a case of a 62-year-old woman who presented with subacute dorso-lumbar pain. A computed tomography (CT) scan reveal

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… We would like to highlight the role of mitotane as the only chemotherapy agent proven to increase overall and recurrence-free survival [ 12 ]. … Metastatic ACC in the spine is exceedingly rare and has no standard curative management yet, although mitotane and local therapeutic measures are currently the treatment of choice in advanced ACC and are not amenable to complete surgical resection. …

An Interesting Case of Hepatic Adrenocortical Carcinoma.

Adrenocortical carcinoma (ACC) is a rare solid tumor with an incidence of 0.5 to 2 cases per million per year. It affects women more commonl … adrenal gland, we planned the patient for surgical resection. Adjuvant treatment with chemotherapy (mitotane and combination of cytotoxic drugs), irradiation might be considered in ACC treatment. To control androgen effects, spironolactone was administered in our patient. However, there was no significant improvement in symptoms.In conclusion, we present t …

Unusual Techniques for Preserving Surgical and Oncologic Safety in Hepatectomy of Advanced Adrenal Malignancy with Vena Cava and Liver Invasion.

BACKGROUND: Status in terms of major vascular structure invasion is a crucial factor for successful major hepatic resection. In particular, … omplication. The patient was discharged 7 days postoperatively and underwent adjuvant chemotherapy (Mitotane) after discharge. Unfortunately, multiple hepatic metastases were identified 4 months after operation. She died 6 months after surgery. In case 2, there was no surgical complication after surgery. The patient was discharged 10 days postoperatively. …

ESMO/ASCO Recommendations for a Global Curriculum in Medical Oncology Edition 2023.

The European Society for Medical Oncology (ESMO) and ASCO are publishing a new edition of the ESMO/ASCO Global Curriculum (GC) with contributions from more than 150 authors. The purpose of the GC is to provide recommendations for the training of physicians in medical oncology and to establish a set of educational standards for trainees to qualify as medical oncologists. This edition builds on prior ones in 2004, 2010, and 2016 and incorporates scientific advances and input from an ESMO/ASCO survey on GC adoption conducted in 2019, which revealed that GC has been adopted or adapted in as many a

Ten years of marketing approvals of anticancer drugs in Europe: regulatory policy and guidance documents need to find a balance between different pressures.

Despite important progress in understanding the molecular factors underlying the development of cancer and the improvement in response rates with new drugs, long-term survival is still disappointing for most common solid tumours. This might be because very little of the modest gain for patients is the result of the new compounds discovered and marketed recently. An assessment of the regulatory agencies' performance may suggest improvements. The present analysis summarizes and evaluates the type of studies and end points used by the EMEA to approve new anticancer drugs, and discusses the applic

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… In one case only, approval was granted without empirical data, on the basis of a bibliographic review of nonclinical and clinical data (mitotane, for adrenal cortical carcinoma). Often a drug was first approved on the basis of preliminary evidence from RNCT. …

ESMO/ASCO Recommendations for a Global Curriculum in Medical Oncology Edition 2023.

The European Society for Medical Oncology (ESMO) and ASCO are publishing a new edition of the ESMO/ASCO Global Curriculum (GC) with contributions from more than 150 authors. The purpose of the GC is to provide recommendations for the training of physicians in medical oncology and to establish a set of educational standards for trainees to qualify as medical oncologists. This edition builds on prior ones in 2004, 2010, and 2016 and incorporates scientific advances and input from an ESMO ASCO survey on GC adoption conducted in 2019, which revealed that GC has been adopted or adapted in as many a

Targeted drug approvals in 2023: breakthroughs by the FDA and NMPA.

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… Narlumosbart | 9/05/2023 | RANKL inhibitor | For the treatment of adult patients with giant cell tumours of bone that are not surgically resectable or whose surgical resection may result in severe functional impairment | Monoclonal antibody (mAb) | Shanghai JMT Biological Technology Co., Ltd. 42 | Lysodren | Mitotane …

Current Status of 68Ga-Pentixafor in Solid Tumours.

Chemokine receptor CXCR4 is overexpressed in neoplasms and its expression is related to tumour invasion, metastasis and aggressiveness. 68Ga-Pentixafor is used to non-invasively image the expression of CXCR4 in tumours and has been widely used in haematological malignancies. Recent evidence shows that therapies targeting CXCR4 can increase the chemosensitivity of the tumour as well as inhibit tumour metastasis and aggressiveness. 68Ga-Pentixafor has shown promise as an elegant radiotracer to aid in the selection of patients whose tumours demonstrate CXCR4 overexpression and who therefore may b

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… Mitotane in combination with chemotherapy is used as a first-line systemic therapy in patients with metastatic disease; however, recurrence is seen in approximately 50%, even after mitotane therapy, and all available systemic therapies are only palliative. …

Hyponatraemia and the syndrome of inappropriate antidiuresis (SIAD) in cancer.

Hyponatraemia is a common electrolyte abnormality seen in a wide range of oncological and haematological malignancies and confers poor performance status, prolonged hospital admission and reduced overall survival, in patients with cancer. Syndrome of inappropriate antidiuresis (SIAD) is the commonest cause of hyponatraemia in malignancy and is characterised by clinical euvolaemia, low plasma osmolality and concentrated urine, with normal renal, adrenal and thyroid function. Causes of SIAD include ectopic production of vasopressin (AVP) from an underlying tumour, cancer treatments, nausea and p

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… Isolated reports of ACTH deficiency causing SIAD-like syndrome Treatment for adrenal carcinoma | Mitotane particularly – usually needs higher maintenance doses of steroid replacement. Cerebral irradiation | ACTH deficiency. …

From bench to bedside: the application of cannabidiol in glioma.

Glioma is the most common malignant tumor in central nervous system, with significant health burdens to patients. Due to the intrinsic characteristics of glioma and the lack of breakthroughs in treatment modalities, the prognosis for most patients remains poor. This results in a heavy psychological and financial load worldwide. In recent years, cannabidiol (CBD) has garnered widespread attention and research due to its anti-tumoral, anti-inflammatory, and neuroprotective properties. This review comprehensively summarizes the preclinical and clinical research on the use of CBD in glioma therapy

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… Pharmacokinetic interaction between mitotane and etoposide in adrenal carcinoma: a pilot study. Endocr Connect. 2018;7(12):1409–1414. doi: 10.1530/EC-18-0428. 111. Riera P, Salazar J, Virgili AC, Tobeña M, Sebio A, Gallano P, et al. …

Gossypol and Its Natural Derivatives: Multitargeted Phytochemicals as Potential Drug Candidates for Oncologic Diseases.

Despite the vast amounts of research and remarkable discoveries that have been made in recent decades, cancer remains a leading cause of death and a major public health concern worldwide. Gossypol, a natural polyphenolic compound derived from the seeds, roots, and stems of cotton (Gossypium hirsutum L.), was first used as a male contraceptive agent. Due to its diverse biological properties, including antifertility, antiviral, antioxidant, antibacterial, antimalarial, and most notably antitumor activities, gossypol has been the subject of numerous studies. Nevertheless, no systematic review has

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… QD or BID | Mild toxicity | PR: 2; SD: 4; PD: 21 No difference in plasma levels between responders and non-responders | [ 121 ] (1993) | Phase I | Adrenal carcinoma ( n = 21) | 30–70 mg racemic gossypol mitotane, and suramine | No serious adverse events | PR: 3 (50% reduction in tumor volume); MR: 1; …

Anticancer Molecular Mechanisms of Curcuminoids: An Updated Review of Clinical Trials.

Curcuminoids are bioactive polyphenols, mainly extracted from Curcuma longa (turmeric), and have received much attention due to their pleiotropic anticancer properties. Recent evidence suggests that curcumin and analogs prevent the activation of a variety of signaling pathways, including the MAPK, PI3K/Akt, and NF-kB pathways, resulting in the induction of apoptosis, prevention of proliferation, and suppression. In addition to these processes, curcumin has been shown to enhance the efficacy of the conventional anti-cancer modalities such as radiation and chemotherapy. By suppressing the expres

Research Communications of the 26th ECVIM‐CA Congress

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Treating Primary Aldosteronism-Induced Hypertension: Novel Approaches and Future Outlooks.

Primary aldosteronism (PA) is the most common cause of secondary hypertension and is associated with increased morbidity and mortality when compared with blood pressure-matched cases of primary hypertension. Current limitations in patient care stem from delayed recognition of the condition, limited access to key diagnostic procedures, and lack of a definitive therapy option for nonsurgical candidates. However, several recent advances have the potential to address these barriers to optimal care. From a diagnostic perspective, machine-learning algorithms have shown promise in the prediction of P

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… The findings of this study preceded an evaluation of the ability of metabolomic profiling to predict the recurrence of ACC, in the presence of corticosteroid replacement and mitotane therapy (which interfere with the interpretation of blood-based assay of cortisol and cortisol metabolism) ( 93 ). …