Antiangiogenic Medications Research Articles

Interdisciplinary management of a patient with medication-related osteonecrosis of the jaw: A clinical report

Medication-related osteonecrosis of the jaw (MRONJ) can be induced by Bisphosphonates (BRONJ), Denosumab, and other antiresorptive or antiangiogenic medications. The number of affected patients with MRONJ is increasing worldwide including in Japan. The treatment often includes surgical resection of necrotic bone and the resulting oral defect impairs oral functions which requires consultation with a maxillofacial prosthodontist before and after surgery for prosthetic rehabilitation. Therefore, there is an urgent need to improve collaboration among different institutions for better patient care. In this report, we emphasize the benefits of such collaboration during the treatment of a female patient with BRONJ in the right maxilla. This patient had breast cancer and received zoledronic acid therapy for the treatment of metastatic osseous lesions. The successful team-based collaboration allowed early restoration of oral functions after surgery using an immediate surgical obturator as well as after delivery of the definitive prosthesis. (Int J Maxillofac Prosthetics 2023;6:16-19)

Potential Use of Thalidomide in Glioblastoma Treatment: An Updated Brief Overview.

Glioblastoma is the most common malignant primary brain tumor in adults. Thalidomide is a vascular endothelial growth factor inhibitor that demonstrates antiangiogenic activity, and may provide additive or synergistic anti-tumor effects when co-administered with other antiangiogenic medications. This study is a comprehensive review that highlights the potential benefits of using thalidomide, in combination with other medications, to treat glioblastoma and its associated inflammatory conditions. Additionally, the review examines the mechanism of action of thalidomide in different types of tumors, which may be beneficial in treating glioblastoma. To our knowledge, a similar study has not been conducted. We found that thalidomide, when used in combination with other medications, has been shown to produce better outcomes in several conditions or symptoms, such as myelodysplastic syndromes, multiple myeloma, Crohn's disease, colorectal cancer, renal failure carcinoma, breast cancer, glioblastoma, and hepatocellular carcinoma. However, challenges may persist for newly diagnosed or previously treated patients, with moderate side effects being reported, particularly with the various mechanisms of action observed for thalidomide. Therefore, thalidomide, used alone, may not receive significant attention for use in treating glioblastoma in the future. Conducting further research by replicating current studies that show improved outcomes when thalidomide is combined with other medications, using larger sample sizes, different demographic groups and ethnicities, and implementing enhanced therapeutic protocol management, may benefit these patients. A meta-analysis of the combinations of thalidomide with other medications in treating glioblastoma is also needed to investigate its potential benefits further.

Synthesis, anti-angiogenic activity and prediction toxicity of (E)-3-(3-methoxyphenyl) propenoic acid.

Anti-angiogenic medications, one of cancer chemo preventive mechanism were permitted for different cancers. Nevertheless, major primary and secondary resistance obstruct efficacy in several tumor types. Moreover, the improvement of safe and effective NSAIDs for angiogenesis inhibition is complicated, because of their serious toxicity. So, we require improving clinically appropriate strategies to boost efficacy of anti-angiogenic drugs with low risk of toxicity. The present study aimed to synthesize the (E)-3- (3-methoxyphenyl)propenoic acid (3MPCA), to determine the anti-angiogenic activity and predict its toxicity. 3MPCA was obtained by Knoevenagel reaction using microwave irradiation at 400 Watt. The anti-angiogenesis experimental was performed using chorioallantois membrane of embryonated chicken eggs induced by b-FGF. The potency of 3MPCA was verified at dosage 30 and 60 ng and compared with celecoxib 60 ng. Toxicity prediction of 3MPCA was performed by ProTox II online program. The results showed that 3MPCA was achieved in good yield (89%). Anti angogenic activity was showed by endothelial cells growth in neovascular capillaries of new blood vessel of chorioallantois membrane of embryonated chicken eggs. The endothelial cells growth decreased until 41.7-83%. The prediction LD50 was 1772mg/kg. (E)-3-(3-methoxyphenyl)propenoic acid can be obtained through Knovenagel reaction using microwave irradiation and it has potential as anti-angiogenesis inhibitor with low toxicity.

Synthesis, anti-angiogenic activity and prediction toxicity of (E)-3-(3-methoxyphenyl) propenoic acid

Background: Anti-angiogenic medications, one of cancer chemo preventive mechanism were permitted for different cancers. Nevertheless, major primary and secondary resistance obstruct efficacy in several tumor types. Moreover, the improvement of safe and effective NSAIDs for angiogenesis inhibition is complicated, because of their serious toxicity. So, we require improving clinically appropriate strategies to boost efficacy of anti-angiogenic drugs with low risk of toxicity. Objectives: The present study aimed to synthesize the (E)-3- (3-methoxyphenyl)propenoic acid (3MPCA), to determine the anti-angiogenic activity and predict its toxicity. Methods: 3MPCA was obtained by Knoevenagel reaction using microwave irradiation at 400 Watt. The anti-angiogenesis experimental was performed using chorioallantois membrane of embryonated chicken eggs induced by b-FGF. The potency of 3MPCA was verified at dosage 30 and 60 ng and compared with celecoxib 60 ng. Toxicity prediction of 3MPCA was performed by ProTox II online program. Results: The results showed that 3MPCA was achieved in good yield (89%). Anti angogenic activity was showed by endothelial cells growth in neovascular capillaries of new blood vessel of chorioallantois membrane of embryonated chicken eggs. The endothelial cells growth decreased until 41.7-83%. The prediction LD50 was 1772mg/kg. Conclusion: (E)-3-(3-methoxyphenyl)propenoic acid can be obtained through Knovenagel reaction using microwave irradiation and it has potential as anti-angiogenesis inhibitor with low toxicity.

Influence of antiresorptive/antiangiogenic therapy on the extension of experimentally induced peri-implantitis lesions

ObjectivesTo investigate the extension of experimentally induced peri-implantitis lesions under various antiresorptive and antiangiogenic medications.Material and methodsFourty-eight albino rats had randomly received the following medications (dual application, n = 8 each): (1) amino-bisphosphonate (zoledronate) (Zo), (2) RANKL inhibitor (denosumab) (De), (3) antiangiogenic (bevacizumab) (Be), (4) Zo+Be, (5) De+Be, or (6) no medication (Co). Ligature- and lipopolysaccharide-induced peri-implantitis lesions were established at 2 maxillary implants over a period of 16 weeks. Histological (e.g., apical extension and surface area of the inflammatory cell infiltrate—aICT, ICT; defect length; defect width; CD68 positive cells) and bone micromorphometric (μCT) outcomes were assessed. The animal was defined as a statistical unit.ResultsA total of n = 38 animals (Zo = 6, De = 6, Be = 8, Zo + Be = 6, De + Be = 5, Co = 7) were analyzed. ICT’s were commonly marked by a positive CD68 antigen reactivity. Comparable median aICT (lowest—Zo: 0.53 mm; highest—Be: 1.22 mm), ICT (lowest—De + Be: 0.00 mm2; highest—Co: 0.49 mm2), defect length (lowest—Zo: 0.90 mm; highest—Co: 1.93 mm) and defect width (lowest—De+Be: 1.27 mm; highest—Be: 1.80 mm) values were noted in all test and control groups. Within an inner (diameter: 0.8 mm) cylindric volume of interest, the bone microstructure did not significantly differ between groups.ConclusionsThe present analysis did not reveal any marked effects of various antiresorptive/ antiangiogenic medications on the extension of experimentally induced peri-implantitis lesions.Clinical relevanceThe extension of peri-implantitis lesions may not be facilitated by the antiresorptive and antiangiogenic medications investigated.

Osteonecrosis of the Jaws due to Drugs: Series of Clinical Cases

Osteonecrosis of the jaw is a rare but severe condition manifested as necrotic bone lesion, it has been linked to the use of potent antiresorptive agents and antiangiogenic medication, in the absence of prior radiation treatment. Staging the pathology once installed, helps us to continue with the protocol guide and is essential to be able to apply the indicated therapy in each case. Clinical Relevance: The contribution of this work is for general dentist, in the observation and clinical management of patients at risk or with development of osteonecrosis of the jaw due to medication, through their staging

Aflibercept suppresses ovarian hyperstimulation syndrome: an experimental study in rats.

In this study, we aimed to determine the impact of the antiangiogenic medications, namely, aflibercept and cabergoline in the prevention and treatment of ovarian hyperstimulation syndrome in a rat model. A total of 36 female Wistar rats were randomly allocated to one of the five groups, including disease-free and ovarian hyperstimulation syndrome controls: Group no OHSS (control, n=6) received saline only intraperitoneally (i.p.); group just OHSS (ovarian hyperstimulation syndrome only, n=6) received 10 IU pregnant mare serum gonadotropin and 30 IU human chorionic gonadotropin subcutaneously to produce ovarian hyperstimulation syndrome; group cabergoline+OHSS (cabergoline+ovarian hyperstimulation syndrome, n=8) received 100 μg/kg oral cabergoline; group aflibercept (12.5 mg/kg)+OHSS (aflibercept+ovarian hyperstimulation syndrome, n=8) received 12.5 mg/kg i.p. aflibercept; and group aflibercept (25 mg/kg)+OHSS (aflibercept+ovarian hyperstimulation syndrome, n=8) received 25 mg/kg i.p. aflibercept. The groups were compared for ovarian weight, immunohistochemical vascular endothelial growth factor expression, spectrophotometric vascular permeability evaluated with methylene blue solution in peritoneal lavage, and body weight growth. Vascular endothelial growth factor immunoexpression was substantially greater in the just OHSS group (22.00±10.20%) than in the aflibercept (12.5 mg/kg)+OHSS (7.87±6.13%) and aflibercept (25 mg/kg)+OHSS (5.63±4.53%) groups (p=0.008 and p=0.005, respectively). Post-hoc tests indicated that cabergoline, 12.5 mg/kg aflibercept, and 25 mg/kg aflibercept decreased vascular permeability compared to the untreated ovarian hyperstimulation syndrome group (p=0.003, p=0.003, and p=0.001, respectively). JOH group had the heaviest ovaries, whereas aflibercept (25 mg/kg)+OHSS group had the lightest. In terms of body weight gain, cabergoline+OHSS group was substantially greater than the aflibercept (12.5 mg/kg)+OHSS and aflibercept (25 mg/kg)+OHSS groups (p=0.006 and p=0.007, respectively). Aflibercept, an antiangiogenic medication, decreased ovarian hyperstimulation syndrome by lowering the vascular permeability and vascular endothelial growth factor expression.

Incidental findings involving the temporomandibular joint on computed tomography and magnetic resonance imaging.

The temporomandibular joint (TMJ) is frequently imaged in head and neck computed tomography (CT) and magnetic resonance imaging (MRI) studies. Depending on the indication for the study, an abnormality of the TMJ may be an incidental finding. These findings encompass both intra- and extra-articular disorders. They may also be related to local, regional or systemic conditions. Familiarity with these findings along with pertinent clinical information helps narrow the list of differential diagnoses. While definitive diagnosis may not be immediately apparent, a systematic approach contributes to improved discussions between clinicians and radiologists and better patient management.

Tislelizumab combined with anlotinib in the second-line treatment of malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a malevolent tumor originated from pleura and often leads to poor prognosis. Chemotherapy of pemetrexed and cisplatin combined with antiangiogenic therapy of bevacizumab is recommended as the first-line regimen by guidelines. However, there are few sustainable second-line anti-tumor theraies that bring distinct survival benefit after the occurrence of drug resistance as the reported mPFS (median progression-free survival) scarcely exceeds 6 months. Immune checkpoint inhibitors are extensively investigated in pan-cancer, and dual immunotherapy has been listed in the first-line recommendation of MPM in several guidelines, while MPM patients benefit modestly from immune checkpoint inhibitors combination or monotherapy in second-line practice. We report a 59-year-old male patient who was diagnosed with unresectable MPM in April 2021. He received firstly pemetrexed combined with platinum and bevacizumab, which barely curbed disease progression; When the first line treatment failed, he was switched to tislelizumab combined with anlotinib. Tislelizumab combined with anlotinib significantly relieved his clinical symptoms, and imaging examination further validated the improvement. Until present, the second-line treatment PFS is more than 10 months. The case firstly demonstrated the efficacy of tislelizumab combined with anlotinib in the second-line management of MPM. Thus, immunotherapy combined with small-molecule multi-target anti-angiogenic medication may be alternative for the second-line schemes of MPM.

The Use of Hydroxyapatite Loaded with Doxycycline (HADOX) in Dentoalveolar Surgery as a Risk-Reduction Therapeutic Protocol in Subjects Treated with Different Bisphosphonate Dosages.

Medication-related osteonecrosis of the jaw (MRONJ) is considered as a severe adverse side effect of specific drugs such as anti-resorptive and anti-angiogenic medications. Evidence suggests that MRONJ is linked to invasive dental procedures, mainly dentoalveolar surgery. Several preventive strategies to minimize the risk of developing MRONJ have been investigated. However, no investigation has been attempted to evaluate the therapeutic effect of local drug-delivery technology as a preventive strategy protocol. The aim of this study is to evaluate the efficacy of hydroxyapatite-containing doxycycline (HADOX) in rats with high-risk MRONJ development. All the rats used in this study were divided into seven groups. Six groups of rats out of seven were exposed to two different doses of antiresorptive drug therapy for four weeks before undergoing an upper incisor extraction. After 28 days, all the animals were euthanized, and the bone blocks were processed for histological and histomorphometrical evaluation. The histomorphometric analysis confirmed that newly formed bone (NFB) was present in all groups, with significant differences. NFB in the HADOX group treated with zoledronic acid at 4% showed (28.38; C.I. 22.29-34.48), which represents a significant increase compared to HA (15.69; C.I. 4.89-26.48) (p = 0.02). A similar pattern was observed in the HADOX group treated with zoledronic acid 8% ZA treatment (p = 0.001). Conclusions: HADOX did not inhibit any bone repair and reduced early inflammatory response. Hence, HADOX could promote bone healing in patients undergoing antiresorptive drug therapy.

The combined use of photobiomodulation therapy and platelet-rich fibrin for the management of two MRONJ stage II cases: An alternative approach

Medication-related osteonecrosis of the jaws (MRONJ) is a relatively rare but serious adverse drug reaction in patients under bone-targeting or antiangiogenic medication for malignant or osteometabolic diseases. The pathogenesis of MRONJ is multifactorial with the inhibition of osteoclasts and angiogenesis considered to play a key role in an individually susceptible environment, thus its prevalence is highly differentiated according to each study. Even though MRONJ has been reported since 2003 and the literature is expanding rapidly about possible risk factors, prevention and treatment options, the successful management with no recurrence is still under controversy. The conservative non-surgical (optimal oral hygiene, systemic antibiotic therapy) and surgical procedures (debridement, sequestrectomy or bone resection) are considered the treatment of choice especially at the early stages. Adjuvant therapies have been proposed to further stimulate bone and tissue healing such as teriparatide, bone morphogenic proteins, platelet concentrates, hyperbaric oxygen, ozone therapy, photodynamic therapy and lasers with promising results. The need to develop minimally invasive treatment protocols using novel technologies in particular for those patients with severe medical histories has been highlighted in the literature. The clinical protocol that has been developed in our dental department, which is effectively contributing to MRONJ management and combines Photobiomodulation therapy (PBMT) with platelet-rich fibrin (A-PRF), will be presented in this article.

A Comprehensive Quality Meta-Review of Genetic and Pharmacogenomic Aspects of Medication-Related Osteonecrosis of The Jaw (MRONJ)

Background: Antiresorptive and antiangiogenic medications can cause a serious adverse effect known as medication-related osteonecrosis of the jaw (MRONJ). In recent years, a new trend of research has emerged emphasizing the potential relation of MRONJ and genetic predisposition. Current evidence-based science of this adverse reaction is associated with poorly performed studies. Additionally, MRONJ research has recently observed a new trend of studies orientated towards the misuse of reviews. This quality meta-review intends to summarize the results of all systematic reviews and meta-analyses that have been published on MRONJ in relation to genetic and pharmacogenomics risk factors. Methods: The research study protocol was registered into the database of the International Network for the Registration of Systematic Reviews and Meta-Analyses (INPLASY) INPLASY202230002. A comprehensive search across several databases (PubMed, EMBASE, MEDLINE, and CINAHL) was conducted to locate multi-language papers published between January 2003 and November 2022. Data were collected from relevant research studies and appraised in accordance with the precise outcomes described in this evaluation. Results: Only five systematic reviews and meta-analyses were analysed in this meta-review. All the reviews included in this research presented qualities mistakes and shortcomings. Two quality assessment tools (Confidence in Evidence from Reviews of Qualitative research (CERQual) and Assessment of Multiple Systematic Reviews 2 (AMSTAR-2)) were used to evaluate each study included in this research. Conclusions: The data evaluated by this meta-review confirmed the poor-quality secondary research underpinning the genetic/pharmacogenomics aspect of MRONJ. Moreover, this study highlighted the many flaws of the current published systematic and meta-analysis studies published so far.

SHP-1/STAT3-Signaling-Axis-Regulated Coupling between BECN1 and SLC7A11 Contributes to Sorafenib-Induced Ferroptosis in Hepatocellular Carcinoma.

Ferroptosis is a type of iron-dependent cell death pertaining to an excess of lipid peroxidation. It has been suggested that sorafenib—an anti-angiogenic medication for hepatocellular carcinoma (HCC)—induces ferroptosis, but the underlying mechanism for this remains largely unknown. We employed siRNA-mediated gene silencing to investigate the role of Src homology region 2 domain-containing phosphatase-1 (SHP-1), following sorafenib treatment, in cystine/glutamate-antiporter-system-Xc−-regulated cystine uptake. Co-immunoprecipitation was also performed to examine the interactions between MCL1, beclin 1 (BECN1), and solute carrier family 7 member 11 (SLC7A11), which functions as the catalytic subunit of system Xc−. The results of this study showed that sorafenib enhanced the activity of SHP-1, dephosphorylated STAT3, downregulated the expression of MCL1 and, consequently, reduced the association between MCL1 and BECN1. In contrast, increased binding between BECN1 and SLC7A11 was observed following sorafenib treatment. The elevated interaction between BECN1 and SLC7A11 inhibited the activity of system Xc−, whereas BECN1 silencing restored cystine intake and protected cells from ferroptosis. Notably, ectopic expression of MCL1 uncoupled BECN1 from SLC7A11 and rescued cell viability by attenuating lipid peroxidation. The results revealed that ferroptosis could be induced in HCC via SHP-1/STAT3-mediated downregulation of MCL1 and subsequent inhibition of SLC7A11 by increased BECN1 binding.

Bevacizumab-Induced Hypertension as a Potential Physiological Clinical Biomarker for Improved Outcomes in Patients With Recurrent Glioblastoma Multiforme: A Systematic Review.

With the advancement in medicine leading to the discovery of anti-vascular endothelial growth factor drugs, numerous oncologists are now commonly using antiangiogenic medications to improve outcomes and attain disease control. Thus, the significance of prognostic and predictive indicators in patient selection has become increasingly imperative. These biomarkers have the capacity to be highly effective and can easily be implemented in various diagnostic and therapeutic settings on a large scale. Overall, it has the potential of significantly decreasing mortality in a fatal disease and possibly achieving partial or complete remission. Many clinical trials have shown the efficacy of bevacizumab in treating malignancies. However, there are currently no known predictive or prognostic biomarkers for bevacizumab in glioblastoma multiforme (GBM). Several clinical studies have evaluated bevacizumab-induced hypertension as a potential marker in patients with different malignancies, including recurrent glioblastoma multiforme (rGBM). This systematic review was performed to determine the association of bevacizumab-induced hypertension with outcomes in patients with advanced brain cancer and to assess whether hypertension (HTN) can be used as a prognostic factor. The review was conducted according to Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, and the databases were searched from January 2012 to June 2022. This review aimed to evaluate six published studies to investigate the relationship between hypertension and the outcomes of patients with rGBM treated with bevacizumab. Among the included publications, four out of six were retrospective and featured a positive result regarding hypertension being used as an independent predictive factor of survival outcomes in rGBM. However, two studies showed negative results. This can be attributed to the limited subsets of patients and the duration of the studies. In conclusion, bevacizumab-induced hypertension may represent a prognostic factor in patients with rGBM.

Oral-Health-Related Quality of Life in Patients with Medication-Related Osteonecrosis of the Jaw: A Prospective Clinical Study.

Medication-related osteonecrosis of the jaw (MRONJ) represents an adverse side effect of antiresorptive and antiangiogenic medications. It is associated with impaired quality of life, oral health, and oral function and can be classified into various stages. The purpose of this prospective clinical study is to evaluate the impact of stages I and II MRONJ on oral-health-related quality of life (OHRQoL) and related parameters. Patients’ OHRQoL, satisfaction with life, oral discomfort, and oral health were assessed using the German version of the Oral Health Impact Profile (OHIP-G49), visual analog scales (VAS), and Satisfaction with Life Scale (SWLS) at baseline (T0), 10 days (T1), and 3 months after treatment (T2) in 36 patients. Data were analyzed using Kolmogorov–Smirnov test, two-way mixed ANOVAs, and follow-up Mann–Whitney U tests. The impact of treatment effects on the original seven OHIP domain structures and the recently introduced four-dimensional OHIP structure were evaluated using linear regression analysis. Thirty-six patients received surgical MRONJ treatment. Before treatment, patients’ perceived OHRQoL, oral discomfort, oral health, and satisfaction with life were negatively affected by MRONJ. Surgical treatment significantly improved OHRQoL and related parameters (all p ≤ 0.012). This improvement was greater in patients with higher impairment at T0. OHRQoL and oral restrictions were still impaired after treatment in patients who needed prosthetic treatment. The four-dimensional structure revealed valuable information beyond the standard seven OHIP domains. Increased awareness of MRONJ risks and an interdisciplinary treatment approach for MRONJ patients are needed.

Osteonecrosis of the jaw in patients taking Atorvastatin: Case series

Osteonecrosis of the jawbones commonly seen in patients taking bisphosphonates, denosumab, and several antiangiogenic medications with several oral factors such as tooth extraction or dental infection. Currently, patients taking Simvastatin, a medication commonly used to treat hypercholesteremia, were reported of developing osteonecrosis of the jaw. Thus, it is important that clinicians know about the risk of osteonecrosis for patients taking this hypercholesteremia medication. It is not known if the undesirable effect only occurs with Simvastatin or other types of statin medication. We report in detail three cases of osteonecrosis of patients taking Atorvastatin calcium, a second-generation statin medication.

Relationship between drug holiday of the antiresorptive agents and surgical outcome of medication-related osteonecrosis of the jaw in osteoporosis patients

A drug holiday of 3 months does not promote separation of sequestra and is not correlated with treatment outcomes after surgical therapy in osteoporosis patients who receive antiresorptive agents and who have medication-related osteonecrosis of the jaw. Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse effect of antiresorptive agents alone or in combination with immune modulators or antiangiogenic medications, in the absence of radiation exposure to the head and neck region. The effectiveness of surgical treatment for MRONJ has been reported, but the timing of the operation remains controversial. The purpose of this study was to clarify whether preoperative drug holidays of antiresorptive agents promote sequestrum separation and improve treatment outcomes in patients who receive low doses of antiresorptive agents. This retrospective study included 173 patients who received low-dose antiresorptive agents and underwent surgical therapy. The effects of a drug holiday on the separation of sequestra and treatment outcomes were analyzed using logistic and Cox regression analyses. Multivariate analysis revealed that administration of an antiresorptive agent for more than 4 years, a high number of lymphocytes, and an extensive osteolytic area were significantly correlated with separation of sequestra, but drug holiday did not promote sequestrum separation. Furthermore, a drug holiday of 90, 120 or 180 days did not show any improvement in treatment outcomes. The drug holiday of the antiresorptive agents for the treatment of MRONJ is unnecessary, and surgical therapy should be performed early.

The Potential of Novel Lipid Agents for the Treatment of Chemotherapy-Resistant Human Epithelial Ovarian Cancer.

Simple SummaryDisease recurrence and chemotherapy resistance are the major causes of mortality for the majority of epithelial ovarian cancer (EOC) patients. Standard of care relies on cytotoxic drugs that induce a form of cell death called apoptosis. EOC cells can evolve to resist apoptosis. We developed drugs called glycosylated antitumor ether lipids (GAELs) that kill EOC cells by a mechanism that does not involve apoptosis. GAELs most likely induce cell death through a process called methuosis. Importantly, we showed that GAELs are effective at killing chemotherapy-resistant EOC cells in vitro and in vivo. Our work shows that the EOC community should begin to investigate methuosis-inducing agents as a novel therapeutic platform to treat chemotherapy-resistant EOC.Recurrent epithelial ovarian cancer (EOC) coincident with chemotherapy resistance remains the main contributor to patient mortality. There is an ongoing investigation to enhance patient progression-free and overall survival with novel chemotherapeutic delivery, such as the utilization of antiangiogenic medications, PARP inhibitors, or immune modulators. Our preclinical studies highlight a novel tool to combat chemotherapy-resistant human EOC. Glycosylated antitumor ether lipids (GAELs) are synthetic glycerolipids capable of killing established human epithelial cell lines from a wide variety of human cancers, including EOC cell lines representative of different EOC histotypes. Importantly, GAELs kill high-grade serous ovarian cancer (HGSOC) cells isolated from the ascites of chemotherapy-sensitive and chemotherapy-resistant patients grown as monolayers of spheroid cultures. In addition, GAELs were well tolerated by experimental animals (mice) and were capable of reducing tumor burden and blocking ascites formation in an OVCAR-3 xenograft model. Overall, GAELs show great promise as adjuvant therapy for EOC patients with or without chemotherapy resistance.

Efficacy of fibrin-rich platelets and leukocytes (L-PRF) in tissue repair in surgical oral procedures in patients using zoledronic acid-case-control study.

IntroductionMedication-related osteonecrosis of the jaws (MRONJ) is a complication that develops in patients who use or have used antiresorptive or antiangiogenic medications for the treatment of bone metabolic disease and bone metastases. Clinically, MRONJ is characterized by the appearance of an inflammation in soft tissues and exposure of necrotic bone tissue in mandible or maxilla, for a period of 8 weeks, in patients with no history of head and neck radiotherapy that were being or are being treated with antiresorptive and/or antiangiogenic agents. The fibrin-rich platelets and leukocytes (L-PRF) membrane has been used as an alternative for MRONJ prevention. The aim of this study was to evaluate the use of L-PRF in prevention and treatment of bone necrosis.Material and MethodsThe patients included had MRONJ diagnosis confirmed after clinical and radiographic examination and patients whose only therapeutic option was dental extraction.ResultsTwenty patients were included in the study and were divided in three groups. Two patients were removed from the study due to previous history of pentoxifylline and tocopherol use. The result of surgical treatment was successful in 57% in group 1 (control/MRONJ prevention), 100% in group 2 (MRONJ prevention), and 80% in group 3 (MRONJ treatment).ConclusionL-PRF is an autologous biomaterial that allows the release of growth factors for a prolonged time, resulting in a better healing, reducing the risk contamination, edema, and postoperative pain, being a great ally in the prevention and treatment of MRONJ because it returns to these patients, mainly quality of life, reducing pain, and recurrent infections commonly seen in the processes of bone necrosis of the jaws.

Oral care principles for older adults: Part 2

##Learning outcomes understand the relevance of state of dependency on treatment planning for older adults; be familiar with the risk management for older patients taking bisphosphonates, anti-angiogenic and anticoagulant medications; and, recognise the need for atraumatic procedures in patients at risk of osteonecrosis.