A Landmark Approach to Aphrodisiac Property of Abelmoschus manihot (L.)

The Abelmoschus manihot (L.) commonly reffered to as “Junglee bhindi” is widely used to control fertility, depression and anxiety in traditional Chinese medicine and has potential therapeutic benefit for cardiovascular diseases associated with diabetes mellitus. The present study is aimed to investigate the effect of 95% ethanolic extract of Abelmoschus manihot on general mounting frequency, intromission frequency, penile erection index along with body weight/organ weight and sperm count on sexually normal male mice. Two doses i.e. 100and 200 mg/kg b.w. of ethanolic extract administered to Swiss albino mice, showed pronounced anabolic and spermatogenic effect in animals of respective groups. There was a remarkable increased in sperm count and penile erection index and also improved sexual behavior of male mice by increased mount and intromission frequency.The result of the present study signatured for sexual enhancing capacity of the drug Abelmoschus manihot is an individual and also holds good aphrodisiac property when compared with standard drug. It was noticed that a 200 mg/kg b.w. dose of Abelmoschus manihot, the performance rate enhances without any side effect. Therefore, the conclusion suggestive that the Abelmoschus manihot will be a drug of choice or alternative therapy for a marketed product. Which may help the population to lead their sexual life perfectly with full of pleasure to interact body, mind and sole.Keywords: Abelmoschus manihot, Aphrodisiac, Mounting frequency, Intromission frequency, Penile erection index

Phase II Trial of Dasatinib for Patients with Acquired Resistance to Treatment with the Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors Erlotinib or Gefitinib

Introduction:Dual inhibition of SRC- and EGFR-dependent pathways may overcome acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for patients with lung adenocarcinoma with EGFR mutations. The SRC inhibitor dasatinib demonstrates antitumor activity in gefitinib-resistant cells lines and xenografts. Dasatinib is tolerable for patients with advanced non-small cell lung cancer, and in combination with erlotinib.Methods:We conducted this phase II study of dasatinib 70 mg twice daily in patients with EGFR-mutant lung adenocarcinoma and acquired resistance to EGFR-TKIs. After a protocol amendment based on evolving data about both drugs, patients received dasatinib at a dose of 100 mg daily with continued erlotinib after developing acquired resistance. Enrolled patients either harbored an activating mutation in EGFR or experienced clinical benefit with single-agent erlotinib or gefitinib, followed by RECIST documented progression while being treated with an EGFR-TKI.Results:Twenty-one patients were enrolled, 9 under the original trial design and 12 after the protocol amendments. We observed no complete or partial responses (0% observed rate, 95% confidence interval: 0–18%). The median time to progression was 0.5 months (range, 0.2–1.8 months) in patients treated with dasatinib and 0.9 months (range, 0.4–5 months) for patients treated with dasatinib and erlotinib in combination. Pleural effusions and dyspnea were frequent toxicities.Conclusions:Dasatinib has no activity in patients with EGFR-mutant lung adenocarcinoma with acquired resistance to erlotinib and gefitinib

IMpower030: Phase III study evaluating neoadjuvant treatment of resectable stage II-IIIB non-small cell lung cancer (NSCLC) with atezolizumab (atezo) + chemotherapy

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Society for Immunotherapy of Cancer (SITC) consensus definitions for resistance to combinations of immune checkpoint inhibitors with chemotherapy

Although immunotherapy can offer profound clinical benefit for patients with a variety of difficult-to-treat cancers, many tumors either do not respond to upfront treatment with immune checkpoint inhibitors (ICIs) or progressive/recurrent disease occurs after an interval of initial control. Improved response rates have been demonstrated with the addition of ICIs to cytotoxic therapies, leading to approvals from the US Food and Drug Administration and regulatory agencies in other countries for ICI-chemotherapy combinations in a number of solid tumor indications, including breast, head and neck, gastric, and lung cancer. Designing trials for patients with tumors that do not respond or stop responding to treatment with immunotherapy combinations, however, is challenging without uniform definitions of resistance. Previously, the Society for Immunotherapy of Cancer (SITC) published consensus definitions for resistance to single-agent anti-programmed cell death protein 1 (PD-1). To provide guidance for clinical trial design and to support analyses of emerging molecular and cellular data surrounding mechanisms of resistance to ICI-based combinations, SITC convened a follow-up workshop in 2021 to develop consensus definitions for resistance to multiagent ICI combinations. This manuscript reports the consensus clinical definitions for combinations of ICIs and chemotherapies. Definitions for resistance to ICIs in combination with targeted therapies and with other ICIs will be published in companion volumes to this paper

Defining a Radiomic Response Phenotype: A Pilot Study using targeted therapy in NSCLC

Medical imaging plays a fundamental role in oncology and drug development, by providing a non-invasive method to visualize tumor phenotype. Radiomics can quantify this phenotype comprehensively by applying image-characterization algorithms, and may provide important information beyond tumor size or burden. In this study, we investigated if radiomics can identify a gefitinib response-phenotype, studying high-resolution computed-tomography (CT) imaging of forty-seven patients with early-stage non-small cell lung cancer before and after three weeks of therapy. On the baseline-scan, radiomic-feature Laws-Energy was significantly predictive for EGFR-mutation status (AUC = 0.67, p = 0.03), while volume (AUC = 0.59, p = 0.27) and diameter (AUC = 0.56, p = 0.46) were not. Although no features were predictive on the post-treatment scan (p > 0.08), the change in features between the two scans was strongly predictive (significant feature AUC-range = 0.74–0.91). A technical validation revealed that the associated features were also highly stable for test-retest (mean ± std: ICC = 0.96 ± 0.06). This pilot study shows that radiomic data before treatment is able to predict mutation status and associated gefitinib response non-invasively, demonstrating the potential of radiomics-based phenotyping to improve the stratification and response assessment between tyrosine kinase inhibitors (TKIs) sensitive and resistant patient populations

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of non-small cell lung cancer (NSCLC)

Lung cancer is the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for over 85% of all cases. Until recently, chemotherapy – characterized by some benefit but only rare durable responses – was the only treatment option for patients with NSCLC whose tumors lacked targetable mutations. By contrast, immune checkpoint inhibitors have demonstrated distinctly durable responses and represent the advent of a new treatment approach for patients with NSCLC. Three immune checkpoint inhibitors, pembrolizumab, nivolumab and atezolizumab, are now approved for use in first- and/or second-line settings for selected patients with advanced NSCLC, with promising benefit also seen in patients with stage III NSCLC. Additionally, durvalumab following chemoradiation has been approved for use in patients with locally advanced disease. Due to the distinct features of cancer immunotherapy, and rapid progress in the field, clinical guidance is needed on the use of these agents, including appropriate patient selection, sequencing of therapies, response monitoring, adverse event management, and biomarker testing. The Society for Immunotherapy of Cancer (SITC) convened an expert Task Force charged with developing consensus recommendations on these key issues. Following a systematic process as outlined by the National Academy of Medicine, a literature search and panel voting were used to rate the strength of evidence for each recommendation. This consensus statement provides evidence-based recommendations to help clinicians integrate immune checkpoint inhibitors into the treatment plan for patients with NSCLC. This guidance will be updated following relevant advances in the field

Pharmacological insights into antioxidants against colorectal cancer: A detailed review of the possible mechanisms

Colorectal cancer (CRC) is ranked as the fourth most lethal and commonly diagnosed cancer in the world ac-cording to the National Cancer Institute’s latest report. Treatment methods for CRC are constantly being studied for advancement, which leads for more clinically effective cancer curing strategy. Patients with prolonged chronic inflammation caused by ulcerative colitis or similar inflammatory bowel disease are known to have high risks of developing CRC. But at a molecular level, oxidative stress due to reactive oxygen species (ROS) is an important trigger for cancer. Hence, in recent years, exogenous antioxidants have been immensely experimented in pre-clinical and clinical trials, considering it as a potential cure for CRC. Significantly, potential antioxidant compounds especially derivatives of medicinal plants have received great attention in the current research trend for CRC treatment. Though antioxidant compounds seem to have beneficial properties for the treatment of CRC, there are also limitations for pure compounds to be tested clinically. Therefore, this review aims to delineate the pharmacological awareness among researchers on using antioxidant compounds to treat CRC and the measures taken to prove the effectiveness of such compounds as impending drug candidates for CRC treatment in modern medication

Role of interleukin-10 (IL-10) in regulation of GABAergic transmission and acute response to ethanol

Mounting evidence indicates that ethanol (EtOH) exposure activates neuroimmune signaling. Alterations in pro-inflammatory cytokines after acute and chronic EtOH exposure have been heavily investigated. In contrast, little is known about the regulation of neurotransmission and/or modulation by anti-inflammatory cytokines in the brain after an acute EtOH exposure. Recent evidence suggests that interleukin-10 (IL-10), an anti-inflammatory cytokine, is upregulated during withdrawal from chronic EtOH exposure. In the present study, we show that IL-10 is increased early (1 h) after a single intoxicating dose of EtOH (5 g/kg, intragastric) in Sprague Dawley rats. We also show that IL-10 rapidly regulates GABAergic transmission in dentate gyrus neurons. In brain slice recordings, IL-10 application dose-dependently decreases miniature inhibitory postsynaptic current (mIPSC) area and frequency, and decreases the magnitude of the picrotoxin sensitive tonic current (I(tonic)), indicating both pre- and postsynaptic mechanisms. A PI3K inhibitor LY294002 (but not the negative control LY303511) ablated the inhibitory effects of IL-10 on mIPSC area and I(tonic), but not on mIPSC frequency, indicating the involvement of PI3K in postsynaptic effects of IL-10 on GABAergic transmission. Lastly, we also identify a novel neurobehavioral regulation of EtOH sensitivity by IL-10, whereby IL-10 attenuates acute EtOH-induced hypnosis. These results suggest that EtOH causes an early release of IL-10 in the brain, which may contribute to neuronal hyperexcitability as well as disturbed sleep seen after binge exposure to EtOH. These results also identify IL-10 signaling as a potential therapeutic target in alcohol-use disorders and other CNS disorders where GABAergic transmission is altered