Novel mutation of PPOX gene in a patient with abdominal pain and syndrome of inappropriate antidiuresis

Abstract

Purpose

Acute porphyrias are metabolic disorders of heme biosynthesis characterized by acute life-threatening attacks. The diagnosis is often missed since clinical presentation is aspecific mimicking other medical and surgical conditions. Variegate porphyria (VP) is an autosomal dominant inherited disease with incomplete penetrance due to decreased activity of the Protoporphyrinogen Oxydase (PPOX) gene; most VP mutations are family specific. We report the case of a 40 year-old woman who presented many times to the emergency department complaining of unexplained abdominal pain and laboratory investigations showed repeatedly hyponatremia. Syndrome of inappropriate antidiuresis (SIAD) was confirmed and measurement of urine porphobilinogen and delta-aminolevulinic acid disclosed the diagnosis of acute porphyria. The genetic analysis of PPOX gene was performed.

Methods

The entire coding sequence and exon/intron boundaries of PPOX gene were amplified in 5 different Polymerase Chain Reaction (PCR) fragments. In silico prediction of the pathogenicity of the mutation was determined by using different tools, Polyphen2, SNPs&GO, SNPs3D.

Results

The genetic analysis of PPOX gene revealed a novel missense variant c.1376 G > A (p.Cys459Tyr) in heterozygous state. The same variant was later found in one of her cousins with skin lesions and other three younger asymptomatic relatives. We provided evidence that this novel mutation is likely to be pathogenetic.

Conclusions

Our case highlights the importance of considering VP in the differential diagnosis of SIAD and underlines the role of genetic screening in the management of such patients. The finding of a novel mutation of PPOX gene in our index case has allowed to recognize an affected family.

https://ift.tt/2FxjtVr

Survival of aggressive variants of papillary thyroid carcinoma in patients under 55 years old: a SEER population-based retrospective analysis

Abstract

Background

Patients younger than 55 years of age with papillary thyroid carcinoma (PTC) have excellent survival. Diffuse sclerosing variant (DSV) and tall cell variant (TCV) of PTC are associated with aggressiveness; the survival of patients <55 years of age with these variants is still unclear. We aim to investigate the clinicopathological features and survival of these variants in the age group <55 years.

Methods

All adult patients (<55 years old) with DSV, TCV and conventional PTC (CPTC) came from the Surveillance, Epidemiology, and End Results program (1988–2013). Kaplan–Meier method and log-rank test were used to analyze the survival. Prognostic factors associated with survival were analyzed by Cox multivariate regression.

Results

There were 280 DSV, 615 TCV, and 56287 CPTC in the age group <55 years. DSV and TCV were associated with multifocality, extrathyroidal extension, lymph node and distant metastasis (all p < 0.05). The 10-year disease-specific survival (DSS) of TCV was worse than CPTC (96.3 vs. 99.4%, p < 0.01), but there was no significant difference between DSV and CPTC (99.5 vs. 99.4%, p > 0.05). Cox multivariate regression showed TCV was the independent predictor of DSS (HR: 5.39, p < 0.01).

Conclusion

In the age group <55 years, DSV and TCV are more likely to exhibit aggressive characteristics than CPTC. Patient <55 years of age with DSV have excellent survival likewise, while patients <55 years of age with TCV carry worse survival. Further investigation for the recurrence risk of patients <55 years with these variants would contribute to optimal clinical management making.

https://ift.tt/2N83jTm

TERTp mutation is associated with a shorter progression free survival in patients with aggressive histology subtypes of follicular-cell derived thyroid carcinoma

Abstract

Purpose

Evaluate the impact of TERTp mutation on the outcomes after initial treatment of 45 patients with thyroid carcinomas derived from follicular cells (TCDFC) with aggressive histology, in which the role of this mutation is not yet well defined.

Methods

Analysis of the presence of TERTp (−124C > T and −146C > T), BRAF (V600E), and NRAS (Q 61R) mutations by Sanger sequencing and analysis of their correlation with the patient's outcomes.

Results

Forty-five patients with aggressive histopathologic variants were included in the study. Of these, 68.9% had aggressive variants of papillary thyroid cancer (PTC), 22.2% had poorly differentiated thyroid carcinoma (PDTC)/insular carcinoma, and 8.9% had invasive follicular thyroid cancer (FTC) with Hurthle cell features (Hurthle cell carcinoma). Lymph node metastases were present in 46.7% and distant metastases in 54.6%. The response to the initial therapy was excellent in 45.5% and structurally incomplete in 50%. During the follow-up period (median of 56 months; 5–360 months), 47.7% presented with disease progression and 17.8% experienced disease-related death. In 53.3% of the cases at least one molecular alteration (TERTp in 33.4%, BRAF in 24.5%, RAS in 8.9%) was detected. In the multivariate analysis, TERTp mutation was the factor associated with the highest risk (6 times) of having structural disease after initial therapy (p = 0.01), followed by vascular invasion (p = 0.02), gross extrathyroidal extension (ETE) (p = 0.02) and distant metastasis (p = 0.04). Regarding mutational status, only TERTp mutation was associated with disease progression, and diminished disease progression-free survival (PFS). The presence of distant metastasis, vascular invasion and gross ETE were significantly associated with the risk of disease progression.

Conclusions

TERTp mutation appears be an indicator of both persistence and progression of structural disease after initial therapy in aggressive variants of TCDFC, and associates with a shorter progression free survival regardless of the therapy employed.

https://ift.tt/2MFXgYQ

Lack of functional remission in Cushing’s syndrome

Abstract

Introduction

Hypercortisolism leads to severe clinical consequences persisting after the onset of remission. These physical sequelae of cortisol exposure are known to profoundly impact the patient's quality of life. As psychological factors may be correlated with this quality of life, our objective was to determine the specific weight of psychological determinants of quality of life in patients in remission from hypercortisolism.

Patients and methods

In an observational study, 63 patients with hypercortisolism in remission were asked to complete exhaustive self-administered questionnaires including quality of life (WHOQoL-BREF and Cushing QoL), depression, anxiety, self-esteem, body image, and coping scales. Multivariate analyses were performed. Psychological variables relevant to the model were: anxiety, depression, self-esteem, body image, and positive thinking dimension of the Brief-COPE. Cortisol deficiency was defined as a potential confounder.

Results

The median time since remission was 3 years. Patients had significantly lower quality of life and body satisfaction score than the French population and patients with chronic diseases. Depression significantly impaired all WHOQoL and Cushing QoL domains. A low body satisfaction score significantly impaired social relationships quality of life score. In total, 42.9% of patients still needed working arrangements, 19% had disability or cessation of work.

Conclusion

Patients in biological remission of hypercortisolism can rarely be considered as functionally cured: this is evidenced by altered quality of life, working arrangements, and chronic depression. A multidisciplinary management of these patients is thus mandatory on a long-term basis.

https://ift.tt/2BFhpdF

Additions of neural monitoring for thyroid surgery

https://ift.tt/2PnIDbp

The posterior pharyngeal wall thickness is associated with OSAHS in patients with acromegaly and correlates with IGF-1 levels

Abstract

Purpose

To evaluate the incidence of obstructive sleep apnea-hypopnea syndrome (OSAHS), explore the structural changes in pharyngeal soft tissue underlying OSAHS development and analyze the correlation between hormone levels and pharyngeal soft tissue changes in patients with untreated acromegaly.

Methods

Twenty-five patients with untreated acromegaly were prospectively enrolled. Pituitary hormones were tested, sellar magnetic resonance imaging was confirmed, overnight polysomnography was conducted, and upper airway computed tomography was performed on these patients.

Results

Patients with untreated acromegaly had a high incidence of OSAHS (52.0%, 13/25). The average age of the patients with OSAHS was 12 years older than that of patients without OSAHS (47.0 ± 8.5 years vs. 35.1 ± 9.5 years, p = 0.003). The posterior pharyngeal soft tissues were thicker in four different planes, including the planes of the soft palate, uvula, tongue and epiglottis (p = 0.003, 0.008, 0.027, and 0.003, respectively), and the soft palate (p = 0.024) was more hypertrophic in patients with acromegaly presenting with OSAHS than patients without OSAHS. The posterior pharyngeal wall thickness (cm) positively correlated with the serum insulin-like growth factor 1 (IGF-1) level (ng/ml) in the planes of the soft palate (slope = 0.001, p = 0.006) and epiglottis (slope = 0.002, p = 0.039).

Conclusions

OSAHS is a common complication in patients with untreated acromegaly, and advanced age is a risk factor. Posterior pharyngeal soft tissue thickening and soft palate hypertrophy are structural changes underlying OSAHS development in patients with acromegaly. Higher IGF-1 levels predict an increase in the posterior pharyngeal soft tissue thickness in patients with acromegaly.

https://ift.tt/2N1v9QN

Pituitary in black—hypopituitarism secondary to hemosiderosis

https://ift.tt/2PoyQla

Incidence and management of postoperative hyperglycemia in patients undergoing insulinoma resection

Abstract

Purpose

It has been proposed that rebound hyperglycemia after resection of insulinoma indicates a biochemical cure. However, there is scant objective data in the literature on the rate and need for intervention in hyperglycemia in patients undergoing resection of insulinoma. The goal of our study was to evaluate the rate of postoperative hyperglycemia, any predisposing factors, and the need for intervention in a prospective cohort study of all patients undergoing routine glucose monitoring.

Methods

A retrospective analysis of 33 patients who had an insulinoma resected and who underwent routine postoperative monitoring of blood glucose (every hour for the first six hours then every four hours for the first 24 h) was performed. Hyperglycemia was defined as glucose greater than 180 mg/dL (10 mmol/l).

Results

Twelve patients (36%) developed hyperglycemia within 24 h (range 1–16 h). In patients with hyperglycemia, the mean maximum plasma glucose level was 221.5 mg/dL (range 97–325 mg/dL) (12.3 mmol/l), and four (33%) patients were treated with insulin. There was no significant difference in age, gender, body mass index (BMI), tumor size, biochemical profile, or surgical approach and extent of pancreatectomy between patients who developed hyperglycemia and those who did not. Pre-excision and post-excision intraoperative insulin levels were evaluated in 14 of 33 patients. The percentage decrease of the intraoperative insulin levels was not significantly different between patients who developed hyperglycemia and those who did not. All patients with postoperative hyperglycemia had normalization of their glucose levels, and none were discharged on anti-hyperglycemic agents.

Conclusions

Hyperglycemia is common after insulinoma resection, and a subset of patients require transient treatment with insulin.

https://ift.tt/2N1WJgU

Histology-proven recurrence in the lateral or central neck after systematic neck dissection for medullary thyroid cancer

Abstract

Purpose

To delineate risk factors for, and examine temporal patterns of, histology-proven recurrent medullary thyroid cancer (MTC) after compartment-oriented surgery.

Methods

Multivariate Cox regression on overall, node, and soft tissue infiltrate recurrence per previously dissected neck compartment.

Results

Mean follow-up for the 203 (and 158) patients with central (and ipsilateral lateral) neck dissection was 56.1 months. On multivariate Cox regression, tumor size > 20 mm predicted overall and node recurrence in the central neck, whereas extranodal growth predicted overall and node recurrence in the ipsilateral lateral neck. Extrathyroidal extension alone predicted soft tissue infiltrate recurrence in the central neck, and extranodal growth alone soft tissue infiltrate recurrence in the ipsilateral lateral neck. When analyses were restricted to patients not biochemically cured after initial surgery, only extranodal growth predicted overall and node recurrence in the dissected neck compartments.

Conclusions

Patients not biochemically cured, specifically those with extranodal growth at the initial operation, carry greater risks of node recurrence.

https://ift.tt/2JplWmW

Patients’ knowledge about the outcomes of thyroid biopsy: a patient survey

Abstract

Purpose

Fine-needle aspiration biopsy of the thyroid is an increasingly common outpatient procedure. Patients are counseled about the indications and risks of this procedure and informed consent is obtained. We aimed to assess the extent to which patients acquired necessary knowledge during this process.

Methods

Survey study conducted in a thyroid nodule clinic at a referral center. Adult patients who had just undergone a thyroid biopsy were asked to complete a survey, including eight questions regarding the indications and potential outcomes of thyroid biopsy. The main outcome of the study was to assess the patients' knowledge based on the response to each individual survey question.

Results

Two-hundred and ninety-seven patients were eligible, of which 196 (66%) completed the survey: most were women (76%), had adequate reading health literacy (95%) and a mean age of 58 years. Although 86% of patients correctly identified evaluation for thyroid cancer as the main indication for their biopsy, 56% were not aware of the likelihood of this diagnosis. Almost all (>90%) of respondents knew that results could be benign or malignant; fewer were aware of non-diagnostic (71%) or indeterminate (68%) outcomes, or of the need for additional diagnostic testing after the biopsy (33%).

Conclusions

After undergoing thyroid biopsy, a high proportion of well-educated patients remained unaware of their risk for thyroid cancer, potential outcomes, and downstream consequences of their biopsy. This quality gap raises the possibility that informed consent procedures that meet legal standards may leave patients undergoing thyroid biopsy paradoxically uninformed.

https://ift.tt/2MqQKWU

Epidemiology of acromegaly in Italy: analysis from a large longitudinal primary care database

Abstract

Purpose

Epidemiological data are pivotal for the estimation of disease burden in populations.

Aim

Of the study was to estimate the incidence and prevalence of acromegaly in Italy along with the impact of comorbidities and hospitalization rates as compared to the general population.

Methods

Retrospective epidemiological study (from 2000 to 2014) and case control-study. Data were extracted from the Health Search Database (HSD). HSD contains patient records from about 1000 general practitioners (GPs) throughout Italy, covering a population of more than 1 million patients. It includes information about patient demographics and medical data including clinical diagnoses and diagnostic tests.

Results

At the end of the study period, 74 acromegaly patients (out of 1,066,871 people) were identified, resulting in a prevalence of 6.9 per 100,000 inhabitants [95% CI 5.4–8.5]. Prevalence was higher in females than men (p = 0.004), and showed a statistically significant trend of increase over time (p < 0.0001). Overall, incidence during the study period was 0.31 per 100,000 person-years. Hypertension and type II diabetes mellitus were the comorbidities more frequently associated with acromegaly (31.3 and 14.6%, respectively) and patients were more likely to undergo a high frequency of yearly hospitalization (≥3 accesses/year, p < 0.001) compared to sex-age matched controls.

Conclusions

This epidemiological study on acromegaly carried out using a large GP-based database, documented a disease prevalence of about 7 cases per 100,000 inhabitants. As expected, acromegaly was associated with a number of comorbidities (mainly hypertension and type II diabetes mellitus) and a high rate of patients' hospitalization.

https://ift.tt/2whcgCn

Role of the ubiquitin/proteasome system on ACTH turnover in rat corticotropes

Abstract

Purpose

A large number of studies has investigated proopiomelanocortin processing in anterior pituitary corticotropes but little is known on proopiomelanocortin/ACTH degradation within these cells. The ubiquitin-proteasome system is an intracellular protein degradation pathway which has garnered considerable interest in recent times, given its role in maintenance of protein homeostasis. Aim of the present study was to evaluate the role of the ubiquitin-proteasome system in proopiomelanocortin/ACTH turnover in pituitary corticotropes.

Methods

Rat anterior pituitary primary cultures were treated with 0.01–100 nM MG132, a proteasome inhibitor, or 0.1–100 nM K48R, an inhibitor of polyubiquitylation, for 4 and 24 h and ACTH concentrations in medium and cell lysates estimated by immunometric assay. Co-immunoprecipitation for ubiquitin and ACTH was carried out to establish ubiquitin-tagged protein products.

Results

Inhibition of proteasome-mediated degradation with MG132 lead to an increase in ACTH concentrations, both as regards secretion and cell content. Likewise, inhibition of polyubiquitylation was associated with increased ACTH secretion and cell content. Ubiquitin/ACTH co-immunoprecipitation revealed that proopiomelanocortin was a target of ubiquitylation.

Conclusions

We provide the first evidence that the ubiquitin-proteasome system is involved in proopiomelanocortin/ACTH degradation in corticotropes. Indeed, proopiomelanocortin is a target of ubiquitylation and modulation of ubiquitin-proteasome system affects ACTH turnover. This study shows that regulation of ACTH proteolytic degradation may represent a means to control ACTH secretion.

https://ift.tt/2PqkiS2

Giant pituitary adenoma: histological types, clinical features and therapeutic approaches

Abstract

Giant pituitary adenomas comprise about 6–10% of all pituitary tumors. They are mostly clinically non-functioning adenomas and occur predominantly in males. The presenting symptoms are usually secondary to compression of neighboring structures, but also due to partial or total hypopituitarism. Functioning adenomas give rise to specific symptoms of hormonal hypersecretion. The use of dopamine agonists is considered a first-line treatment in patients with giant macroprolactinomas. Somatostatin analogs can also be used as primary treatment in cases of growth hormone and thyrotropin producing giant adenomas, although remission of the disease is not achieved in the vast majority of these patients. Neurosurgical treatment, either through transsphenoidal or transcranial surgery, continues to be the treatment of choice in the majority of patients with giant pituitary adenomas. The intrinsic complexity of these tumors requires the use of different therapies in a combined or sequential way. A multimodal approach and a therapeutic strategy involving a multidisciplinary team of expert professionals form the basis of the therapeutic success in these patients.

https://ift.tt/2wb1PjM

A review on the direct effect of particulate atmospheric pollution on materials and its mitigation for sustainable cities and societies

Abstract

Particulate matter (PM) has gained significant attention due to the increasing concerns related to their effects on human health. Although several reviews have shed light on the effect of PM on human health, their critical adverse effect on material's structure and sustainability was almost neglected. The current study is an attempt to fill this gap related to PM impact on structural materials under the overall consideration of sustainability. More specifically, this review highlights the existing knowledge by providing an overview on PM classification, composition, and sources in different locations around the world. Then, it focuses on PM soiling of surfaces such as solar panels due to an increasing need to mitigate the impact of soiling on reducing photovoltaic (PV) power output and financial competitiveness in dusty regions. This topic is of critical importance for sustainable deployment of solar energy in arid and desert areas around the world to help in reducing their impact on overall climate change and life quality. In addition, this review summarizes climate change phenomena driven by the increase of PM concentration in air such as radiative forcing and acid rain deposition due to their impact on human health, visibility and biodiversity. To this end, this work highlights the role of process management, choice of fuel, the implementation of clean technologies and urban vegetation as some possible sustainable mitigation policies to control PM pollution in cities and urban regions. This research is designed to conduct a comprehensive narrative literature review which targets broad spectrum of readers and new researchers in the field. Moreover, it provides a critical analysis highlighting the need to fill main research gaps in this domain. The findings of this review paper show that PM pollution imposes severe adverse impacts on materials, structures and climate which directly affect the sustainability of urban cities. The advantages of this review include the value of the extensive works that elaborate on the negative impacts of PM atmospheric pollution towards high level of public awareness, management flexibility, stakeholder's involvements, and collaboration between academy, research, and industry to mitigate PM impact on materials and human welfare.

https://ift.tt/2LcKE77

Potential sources and meteorological factors affecting PM 2.5 -bound polycyclic aromatic hydrocarbon levels in six main cities of northeastern Italy: an assessment of the related carcinogenic and mutagenic risks

Abstract

A yearlong sampling campaign (2012–2013) was conducted in six major cities of the Veneto region to investigate the spatial-temporal trends and the factors affecting the polycyclic aromatic hydrocarbon (PAHs) variations and identify the local sources. Sixty samples per city were collected for analyses in every alternate month (April, June, August, October, December, and February): 10 samples per sampling site in 10 consecutive days of the months selected. Samples were ultrasonically extracted with acetonitrile and processed through high-performance liquid chromatography. Total Σ-PAH concentrations ranged from 0.19 to 70.4 ng m⁻³ with a mean concentration of 11.5 ng m⁻³. The mean benzo[a]pyrene (BaP) concentration reached 2.0 ng m⁻³, which is two-times higher than the limit set by the European Union. BaP contributed for 17.4% to the total concentration of PAHs, which showed the same pattern across the region with maxima during cold months and minima in the warm period. In this study, PAHs showed an inverse relationship with temperature, solar radiation, wind speed, and ozone. According to this study, biomass burning for household heating and cooking, followed by gaseous PAHs absorption on particles due to low atmospheric temperature, were the main reasons for increasing PAHs concentration in winter. Health risk, evaluated as lifetime lung cancer risk (LCR), showed a potential carcinogenic risk from the airborne BaP_TEQ six-fold higher in the cold season than in the warm one. Diagnostic ratios and conditional probability functions were used to locate the sources, and results confirmed that local emission, overall domestic heating, and road transport exhausts were responsible for higher concentration rates of PAHs as well as of PM_2.5.

https://ift.tt/2vTSLk3

Treating MTBE-contaminated water using sewage sludge-derived activated carbon

Abstract

In this study, sewage sludge-derived activated carbon (SDAC) was synthesized, characterized, and tested for its potential as an adsorbent of methyl tert-butyl ether (MTBE). The SDAC was produced by activating the sludge with zinc chloride and subsequently subjected to various ranges of pyrolytic temperatures. It was then characterized using SEM/EDX, BET, and TGA. The SEM-EDX analyses showed that impurities like Fe, Al, Mg, Mn, Ca, and Na of the raw sludge were removed by the higher pyrolytic temperature and acid-washing procedures. TGA showed the thermal stability of the produced material. Results of the BET revealed a significant increase in surface area of the sludge from 1.5 m²/g to 385 m²/g after acid washing. The MTBE removal efficiency of 70% was achieved after 60 min with 2 g/L of SDAC at pH 6, and initial MTBE concentration of 1 ppm. The adsorption kinetics of SDAC fitted into pseudo-second-order reactions. This work demonstrated a beneficial use of a bio-waste material (sewage sludge) in water treatment technologies.

https://ift.tt/2LcLPDo

Immunological-based approaches for cancer therapy

The immunologic landscape of tumors has been continuously unveiled, providing a new look at the interactions between cancer cells and the immune system. Emerging tumor cells are constantly eliminated by the immune system, but some cells establish a long-term equilibrium phase leading to tumor immunoediting and, eventually, evasion. During this process, tumor cells tend to acquire more mutations. Bearing a high mutation burden leads to a greater number of neoantigens with the potential to initiate an immune response. Although many tumors evoke an immune response, tumor clearance by the immune system does not occur due to a suppressive tumor microenvironment. The mechanisms by which tumors achieve the ability to evade immunologic control vary. Understanding these differences is crucial for the improvement and application of new immune-based therapies. Much effort has been placed in developing in silico algorithms to predict tumor immunogenicity and to characterize the microenvironment via high-throughput sequencing and gene expression techniques. Each sequencing source, transcriptomics, and genomics yields a distinct level of data, helping to elucidate the tumor-based immune responses and guiding the fine-tuning of current and upcoming immune-based therapies. In this review, we explore some of the immunological concepts behind the new immunotherapies and the bioinformatic tools to study the immunological aspects of tumors, focusing on neoantigen determination and microenvironment deconvolution. We further discuss the immune-based therapies already in clinical use, those underway for future clinical application, the next steps in immunotherapy, and how the characterization of the tumor immune contexture can impact therapies aiming to promote or unleash immune-based tumor elimination.

https://ift.tt/2vVWQ74

Homologous recombination deficiency in ovarian cancer: a review of its epidemiology and management

Ovarian cancer patients with homologous recombination deficiencies exhibit specific clinical behaviors, and improved responses to treatments, such as platinum-based chemotherapy and poly (ADP-ribose) polymerase (PARP) inhibitors, have been observed. Germline mutations in the BRCA 1/2 genes are the most well-known mechanisms of homologous recombination deficiency. However, other mechanisms, such as germline and somatic mutations in other homologous recombination genes and epigenetic modifications, have also been implicated in homologous recombination deficiency. The epidemiology and implications of these other mechanisms need to be better understood to improve the treatment strategies for these patients. Furthermore, an evaluation of various diagnostic tests to investigate homologous recombination deficiency is essential. Comprehension of the role of homologous recombination deficiency in ovarian cancer also allows the development of therapeutic combinations that can improve the efficacy of treatment. In this review, we discuss the epidemiology and management of homologous recombination deficiency in ovarian cancer patients.

https://ift.tt/2OLzI28

Improving adenoviral vectors and strategies for prostate cancer gene therapy

Gene therapy has been evaluated for the treatment of prostate cancer and includes the application of adenoviral vectors encoding a suicide gene or oncolytic adenoviruses that may be armed with a functional transgene. In parallel, versions of adenoviral vector expressing the p53 gene (Ad-p53) have been tested as treatments for head and neck squamous cell carcinoma and non-small cell lung cancer. Although Ad-p53 gene therapy has yielded some interesting results when applied to prostate cancer, it has not been widely explored, perhaps due to current limitations of the approach. To achieve better functionality, improvements in the gene transfer system and the therapeutic regimen may be required. We have developed adenoviral vectors whose transgene expression is controlled by a p53-responsive promoter, which creates a positive feedback mechanism when used to drive the expression of p53. Together with improvements that permit efficient transduction, this new approach was more effective than the use of traditional versions of Ad-p53 in killing prostate cancer cell lines and inhibiting tumor progression. Even so, gene therapy is not expected to replace traditional chemotherapy but should complement the standard of care. In fact, chemotherapy has been shown to assist in viral transduction and transgene expression. The cooperation between gene therapy and chemotherapy is expected to effectively kill tumor cells while permitting the use of reduced chemotherapy drug concentrations and, thus, lowering side effects. Therefore, the combination of gene therapy and chemotherapy may prove essential for the success of both approaches.

https://ift.tt/2w0lIL9

Marine drugs for cancer: surfacing biotechnological innovations from the oceans

This review will discuss the contributions of marine natural molecules, a source only recently found to have pharmaceutical prospects, to the development of anticancer drugs. Of the seven clinically utilized compounds with a marine origin, four are used for the treatment of cancer. The development of these drugs has afforded valuable knowledge and crucial insights to meet the most common challenges in this endeavor, such as toxicity and supply. In this context, the development of these compounds will be discussed herein to illustrate, with successful examples provided by cytarabine, trabectedin, eribulin and brentuximab vedotin, the steps involved in this process as well as the scientific advances and technological innovation potential associated with developing a new drug from marine resources.

https://ift.tt/2ON77to