Hypoactive Sexual Desire Disorder (HSDD) is the most common form of Female Sexual Dysfunction and is characterized by low sexual desire that causes distress.
The aim of this study was to assess the ...efficacy and safety of flibanserin, a postsynaptic 5‐HT1A agonist/5‐HT2A antagonist, in premenopausal women with HSDD.
North American premenopausal women with HSDD were randomized to 24 weeks' treatment with placebo (N = 295), flibanserin 50 mg (N = 295), or flibanserin 100 mg (N = 290), once daily at bedtime.
Coprimary endpoints were change from baseline to study end in number of satisfying sexual events (SSE) and sexual desire score measured daily using an electronic diary (eDiary). Secondary endpoints included change from baseline to study end in Female Sexual Function Index (FSFI) desire domain and total scores, Female Sexual Distress Scale‐Revised (FSDS‐R) Item 13 and total scores, and Patient's Global Impression of Improvement.
Flibanserin 50 mg and 100 mg led to increases in SSE (P < 0.05 and P < 0.01 vs. placebo, respectively). There was a numerical trend toward improvement in eDiary desire score on flibanserin 100 mg, but statistical significance was not reached (P = 0.07 vs. placebo). FSFI desire domain and total scores increased with both flibanserin regimens (P < 0.05). FSDS‐R total and Item 13 scores decreased with flibanserin 100 mg (P < 0.001), indicating reduced sexual distress. More women receiving flibanserin 50 mg and 100 mg considered their HSDD to have improved than women receiving placebo (39.6% and 50.0% vs. 30.3%, respectively) (P < 0.05).
In premenopausal women with HSDD, flibanserin 50 mg and 100 mg once daily at bedtime were well tolerated and associated with statistically significant improvements in SSE, sexual desire (FSFI desire domain score but not eDiary desire score) and overall sexual function, and reduction of sexual distress, vs. placebo. DeRogatis LR, Komer L, Katz M, Moreau M, Kimura T, Garcia Jr. M, Wunderlich G, and Pyke R on behalf of the VIOLET trial investigators. Treatment of Hypoactive Sexual Desire Disorder in premenopausal women: Efficacy of flibanserin in the VIOLET study. J Sex Med 12;9:1074–1085.
Nanotechnology has opened up a new, previously unimaginable world in cancer diagnosis and therapy, leading to the emergence of cancer nanomedicine and nanoparticle-aided radiotherapy. Smart ...nanomaterials (nanoparticle drones) can now be constructed with capability to precisely target cancer cells and be remotely activated with radiation to emit micrometer-range missile-like electrons to destroy the tumor cells. These nanoparticle drones can also be programmed to deliver therapeutic payloads to tumor sites to achieve optimal therapeutic efficacy. In this article, we examine the state-of-the-art and potential of nanoparticle drones in targeting lung cancer. Inhalation (INH) (air) versus traditional intravenous ("sea") routes of navigating physiological barriers using such drones is assessed. Results and analysis suggest that INH route may offer more promise for targeting tumor cells with radiosensitizers and cannabinoids from the perspective of maximizing damage to lung tumors cells while minimizing any collateral damage or side effects.
Radiation therapy induces immunogenic cell death, which can theoretically stimulate T cell priming and induction of tumor-specific memory T cell responses, serving as an
vaccine. In practice, this ...abscopal effect is rarely observed. We use two mouse models of pancreatic cancer to show that a single dose of stereotactic body radiation therapy (SBRT) synergizes with intratumoral injection of agonistic anti-CD40, resulting in regression of non-treated contralateral tumors and formation of long-term immunologic memory. Long-term survival was not observed when mice received multiple fractions of SBRT, or when TGFβ blockade was combined with SBRT. SBRT and anti-CD40 was so effective at augmenting T cell priming, that memory CD8 T cell responses to both tumor and self-antigens were induced, resulting in vitiligo in long-term survivors.
In efforts to overcome current challenges in cancer treatment, multifunctional nanoparticles are attracting growing interest, including nanoparticles made with polydopamine (PDA). PDA is a ...nature-inspired polymer with a dark brown color. It has excellent biocompatibility and is biodegradable, offering a range of extraordinary inherent advantages. These include excellent drug loading capability, photothermal conversion efficiency, and adhesive properties. Though the mechanism of dopamine polymerization remains unclear, PDA has demonstrated exceptional flexibility in engineering desired morphology and size, easy and straightforward functionalization, etc. Moreover, it offers enormous potential for designing multifunctional nanomaterials for innovative approaches in cancer treatment. The aim of this work is to review studies on PDA, where the potential to develop multifunctional nanomaterials with applications in photothermal therapy has been demonstrated. Future prospects of PDA for developing applications in enhancing radiotherapy and/or immunotherapy, including for image-guided drug delivery to boost therapeutic efficacy and minimal side effects, are presented.
Despite technological advances in radiation therapy for cancer treatment, many patient populations still experience mediocre survival percentages, local control, and quality of life. Additionally, ...much of the world lacks access to expensive, modern treatment options. The need for innovative, cost-effective solutions that can improve patient treatment outcomes is essential. Phytomedicines have been shown to induce apoptotic tumor cell death, diminish tumor progression, reduce cancer incidence, alleviate harmful hypoxic conditions, and more. While an ample amount of research is available that characterizes many phytomedicines as having anti-cancer properties that increase tumor cell killing/control and mitigate the harmful side effects of radiation damage, little work has been done to investigate the synergistic effect of phytoradiotherapy: combining radiation treatment with phytomedicines. In this study, a protocol for testing the radiosensitizing effects of phytomedicines was validated and used to investigate the well-known plant based medicine cannabidiol (CBD) and the lesser-known medicinal fruit Bitter Melon. Additionally, based on its high concentration of plant hemoglobin which has been shown to abate hypoxia, the African-indigenous
plant was tested in pancreatic adenocarcinoma mouse models. The studies reveal that these phytomedicines can effectively enhance tumor cell killing, minimize tumor growth, and prolong mice survival. There is certainly the need for additional research in this regard, however, phytoradiotherapy: the use of phytomedicines to enhance radiation therapy treatment outcomes, continues to show potential as a promising, innovative way to improve cancer care.
Indigenous populations use plants as an important healthcare resource or remedy for different diseases. Here, isolated extracts from
(family Acanthanceae) plant leaves used in Africa as remedy for ...anemia are characterized by different methods to assess composition and potential nutritional or therapeutic value. Extracts from
leaves were obtained by aqueous extraction, with further isolation by centrifuging and high-performance liquid chromatography. Extracts and isolated compounds were characterized by ultraviolet-visible (UV-Vis) spectroscopy and inductively coupled plasma mass spectrometry (ICP-MS). Hemoglobin activity was assessed using different hemoglobin assays (Cayman Chemical, and Sigma-Aldrich), as well as ELISA. In addition, the safety of the isolated samples was assessed in vitro and in vivo in mice. ICP-MS study results revealed many essential metabolites found in blood plasma. The UV-Vis spectroscopy results highlighted the presence of hemoglobin, with assays showing levels over 4 times higher than that of similar mass of lyophilized human hemoglobin. Meanwhile, in vivo studies showed faster recovery from anemia in mice administered with the isolated extracts compared to untreated mice. Moreover, in vitro and in vivo studies highlighted safety of the extracts. This study reveals the presence of high levels of elements essential for blood health in the isolated extracts from
plant leaves. The findings inspire further research with the potential applications in food fortification, and as remedy for blood disorders like anemia, which disproportionally affects cancer patients, pregnant women, and populations in low- and middle-income countries.
Pancreatic cancer is particularly refractory to modern therapies, with a 5-year survival rate for patients at a dismal 8%. One of the significant barriers to effective treatment is the ...immunosuppressive pancreatic tumor microenvironment and development of resistance to treatment. New treatment options to increase both the survival and quality of life of patients are urgently needed. This study reports on a new non-cannabinoid, non-psychoactive derivative of cannabis, termed FBL-03G, with the potential to treat pancreatic cancer.
results show major increase in apoptosis and consequential decrease in survival for two pancreatic cancer models- Panc-02 and KPC pancreatic cancer cells treated with varying concentrations of FBL-03G and radiotherapy. Meanwhile,
results demonstrate therapeutic efficacy in delaying both local and metastatic tumor progression in animal models with pancreatic cancer when using FBL-03G sustainably delivered from smart radiotherapy biomaterials. Repeated experiments also showed significant (
< 0.0001) increase in survival for animals with pancreatic cancer compared to control cohorts. The findings demonstrate the potential for this new cannabis derivative in the treatment of both localized and advanced pancreatic cancer, providing impetus for further studies toward clinical translation.
Fiducials are routinely used to provide image-guidance during radiotherapy. Here, a new nanoparticle-based liquid immunogenic fiducial is investigated for its potential to provide image-guidance, ...while also enhancing treatment outcomes.
This fiducial, liquid immunogenic fiducial eluter (LIFE) biomaterial, is formulated with natural biodegradable polymers, chitosan and sodium alginate with radio-sensitizing nanoparticles, and immunoadjuvant like anti-CD40 monoclonal antibody. Once administered intra-tumorally, this liquid smart radiotherapy biomaterial congeals within the calcium rich tumor microenvironment. The potential use of LIFE biomaterial for providing image guidance in magnetic resonance imaging (MRI) and computed tomography (CT) was investigated over different time period in a pre-clinical tumored mouse model.
Results showed that the LIFE biomaterial can provide both MRI contrast and CT imaging contrast over 3-weeks, with gradual decrease of the contrast over time, as the LIFE biomaterial biodegrades. Results also showed the LIFE biomaterial significantly slowed tumor growth and prolonged mice survival (p < 0.0001) over time.
The results highlight the potential use of the LIFE biomaterial as a multi-functional smart radiotherapy biomaterial that could be developed and optimized for hypo-fractionated radiotherapy applications and combining radiotherapy with immunoadjuvants.
In this study, we investigate the use of multifunctional smart radiotherapy biomaterials (SRBs) loaded with immunoadjuvants for boosting the abscopal effect of local radiotherapy (RT). SRBs were ...designed similar to currently used inert RT biomaterials, incorporating a biodegradable polymer with reservoir for loading payloads of the immunoadjuvant anti-CD40 monoclonal antibody. Lung (LLC1) tumors were generated both on the right and left flank of each mouse, with the left tumor representing metastasis. The mice were randomized and divided into eight cohorts with four cohorts receiving image-guided RT (IGRT) at 5 Gy and another similar four cohorts at 0 Gy. IGRT and Computed Tomography (CT) imaging were performed using a small animal radiation research platform (SARRP). Tumor volume measurements for both flank tumors and animal survival was assessed over 25 weeks. Tumor volume measurements showed significantly enhanced inhibition in growth for the right flank tumors of mice in the cohort treated with SRBs loaded with CD40 mAbs and IGRT. Results also suggest that the use of polymeric SRBs with CD40 mAbs without RT could generate an immune response, consistent with previous studies showing such response when using anti-CD40. Overall, 60% of mice treated with SRBs showed complete tumor regression during the observation period, compared to 10% for cohorts administered with anti-CD40 mAbs, but no SRB. Complete tumor regression was not observed in any other cohorts. The findings justify more studies varying RT doses and quantifying the immune-cell populations involved when using SRBs. Such SRBs could be developed to replace currently used RT biomaterials, allowing not only for geometric accuracy during RT, but also for extending RT to the treatment of metastatic lesions.
Globally, cervical cancer is the fourth leading cancer among women and is dominant in resource-poor settings in its occurrence and mortality. This study focuses on developing liquid immunogenic ...fiducial eluter (LIFE) Biomaterial with components that include biodegradable polymers, nanoparticles, and an immunoadjuvant. LIFE Biomaterial is designed to provide image guidance during radiotherapy similar to clinically used liquid fiducials while enhancing therapeutic efficacy for advanced cervical cancer. C57BL6 mice were used to grow subcutaneous tumors on bilateral flanks. The tumor on one flank was then treated using LIFE Biomaterial prepared with the immunoadjuvant anti-CD40, with/without radiotherapy at 6 Gy. Computed tomography (CT) and magnetic resonance (MR) imaging visibility were also evaluated in human cadavers. A pharmacodynamics study was also conducted to assess the safety of LIFE Biomaterial in healthy C57BL6 female mice. Results showed that LIFE Biomaterial could provide both CT and MR imaging contrast over time. Inhibition in tumor growth and prolonged significant survival (*
< 0.05) were consistently observed for groups treated with the combination of radiotherapy and LIFE Biomaterial, highlighting the potential for this strategy. Minimal toxicity was observed for healthy mice treated with LIFE Biomaterial with/without anti-CD40 in comparison to non-treated cohorts. The results demonstrate promise for the further development and clinical translation of this approach to enhance the survival and quality of life of patients with advanced cervical cancer.
PDF
