Investigation of Chemopreventive and Antiproliferative Potential of Dicliptera roxburghiana

Context: Carcinogenesis causes much human misery. It is a process involving multistage alterations. Medicinal plants are candidates for beneficial anticancer agents. Objectives: Investigation of anticancer proficiencies of the plant Dicliptera roxburghiana. Material and methods: Crude extract and derived fractions were inspected for their inhibitory potential against nuclear factor KB (NFκB), nitric oxide synthase inhibition, aromatase inhibition and induction of quinone reductase 1 (QR 1). Antiproliferative activity was determined by using various cancer cell lines for example hormone responsive breast cancer cell line MCF-7, estrogen receptor negative breast cancer cell line MDA-MB-231, murine hepatoma cells Hepa 1c1c7, human neuroblastoma cells SK-N-SH and neuroblastoma cells MYCN-2. Results: Ethyl acetate and n-butanol fractions of D. roxburghiana were strongly active against NFκB with IC50 of 16.6 ± 1.3 and 8.4 ± 0.7 µg/ml respectively with 100% survival. Chloroform fraction of the plant exhibited an induction ratio of 2.4 ± 0.09 with CD value of 17.7 µg/ml. Regarding the nitrite assay, the n-hexane fraction exhibited significant inhibition of NO activity with IC50 of 17.8 ± 1.25 µg/ml. The n-butanol fraction exhibited strong antiproliferative activity against IcIc-7 cell lines with IC50 values of 13.6 ± 1.91 µg/ml; against MYCN-2 a cytotoxic effect developed with dose dependence, with IC50 of 12.6 ± 1.24 µg/ml. In antiproliferative activity against SK-N-SH cell lines, chloroform, ethyl acetate and n-butanol fractions were efficiently active with IC50 values of 11.2 ± 0.84, 14.6 ± 1.71 and 16.3 ± 1.57 respectively. Discussion and Conclusion: It was demonstrated that various fractions of D. roxburghiana displayed appreciable anticancer characteristics and could be a potent source for the development of anticancer leads.

A Case Study Using Papaya Leaf Extract to Reverse Chemotherapy-Induced Thrombocytopenia in a GBM Patient

Chemotherapy-induced thrombocytopenia (CIT) is a critical condition in which platelet counts are abnormally reduced following the administration of chemotherapeutic compounds. CIT poses a treatment conundrum to clinicians given the increased risk of spontaneous bleeding, obstacles to surgical management of tumors, and exclusion from clinical trials. Treatment of CIT involves the removal of the offending agent combined with platelet infusion or thrombopoietin agonist treatment. However, due to the autoimmune and infection risks associated with infusions, this treatment is only reserved for patients with critically low platelet counts. One potential solution for patients in the mid to low platelet count range is Carica papaya leaf extract (CPLE). In this case, we report the novel use of CPLE as a method of bolstering platelet counts in a patient presenting with CIT. The patient was initiated on CPLE therapy consisting of 1 tablespoon twice daily with meals. Following CPLE treatment, the patient’s platelet counts rebounded from less than 10,000/µL to 113,000/µL. This clinical vignette supports the use of CPLE in the clinical context of CIT when thrombopoietin agonists are not a viable option. The potential benefits of CPLE as a method for increasing platelet count deserve further exploration, especially as a treatment option for refractory patients or those ill-suited for other traditional thrombocytopenia therapies.

Therapeutic Potential of Emodin for Gastrointestinal Cancers

Gastrointestinal (GI) cancers cause one-third of all cancer-related deaths worldwide. Natural compounds are emerging as alternative or adjuvant cancer therapies given their distinct advantage of manipulating multiple pathways to both suppress tumor growth and alleviate cancer comorbidities; however, concerns regarding efficacy, bioavailability, and safety are barriers to their development for clinical use. Emodin (1,3,8-trihydroxy-6-methylanthraquinone), a Chinese herb-derived anthraquinone, has been shown to exert anti-tumor effects in colon, liver, and pancreatic cancers. While the mechanisms underlying emodin’s tumoricidal effects continue to be unearthed, recent evidence highlights a role for mitochondrial mediated apoptosis, modulated stress and inflammatory signaling pathways, and blunted angiogenesis. The goals of this review are to (1) highlight emodin’s anti-cancer properties within GI cancers, (2) discuss the known anti-cancer mechanisms of action of emodin, (3) address emodin’s potential as a treatment complementary to standard chemotherapeutics, (4) assess the efficacy and bioavailability of emodin derivatives as they relate to cancer, and (5) evaluate the safety of emodin.

The Association of Sources of Support, Types of Support and Satisfaction with Support Received on Perceived Stress and Quality of Life of Cancer Patients

Introduction: The aim of the present study is to carry out a multidimensional analysis of the relationship of social support with quality of life and the stress perceived by cancer patients. Methods: The participants were 200 patients with cancer. Data was gathered on sociodemographic characteristics, health, quality of life, social support and perceived stress. Results: Frequency of and satisfaction with different sources and types of support are related positively with improvement of quality of life and negatively with perceived stress. The emotional support from the partner and the emotional and informational support from the family are significant predictors of quality of life. Emotional support from the family reduces patients’ perceived stress. Satisfaction with emotional support from the partner and with the informational support from friends and family increases quality of life. Satisfaction with emotional support from the family and with informational support from friends decreases patients’ perceived stress. Instrumental support and support provided by health professionals are not good predictors of quality of life and perceived stress. Satisfaction with the support received is more significantly related with quality of life and stress than the frequency with which the sources provide support. Conclusions: These results have important practical implications to improve cancer patients’ quality of life and reduce their perceived stress through social support. Designing intervention strategies to improve satisfaction with the support provided to patients by their closest networks results in a global benefit for the patient’s quality of life.

A Randomized, Controlled, Parallel-Group, Trial on the Effects of Melatonin on Fatigue Associated with Breast Cancer and Its Adjuvant Treatments

Objective: Fatigue associated with malignant conditions and their treatments is a disabling condition. This trial assessed the anti-fatigue effects of melatonin coadministration during adjuvant treatment of patients with the breast cancer. Material and Methods: Patients with breast cancer were randomly assigned to receive melatonin or placebo during adjuvant chemotherapy and radiotherapy. Thirty-seven patients were randomly enrolled in each group. The mean ages of patients in the intervention and control groups were 50.47 ± 10.79 and 46.05 ± 10.55 years, respectively ( P = .223). The intervention group received oral melatonin (18 mg/day) from 1 week before until 1 month after the adjuvant radiotherapy. The level of fatigue was assessed before and after intervention using Brief Fatigue Inventory (BFI) in both groups. To analyze data, the Student’s t-test and the Chi-square test were used at a significance level of P ≤ .05. Results: The BFI score was similar before the intervention in both groups, however, after the intervention, it was significantly lower in the melatonin group ( P < .001). Moreover, the frequency of severe fatigue in the melatonin group was significantly lower than in the placebo group after intervention (42.1% vs 83.3%, P < .001). Conclusion: Coadministration of melatonin during adjuvant chemotherapy and radiotherapy of women with breast cancer decreased the levels of fatigue associated with the malignant condition and its treatments.

Effects of Cognitive Behavioral Therapy for Depression and Anxiety, Response Rates and Adverse Events in Patients with Locoregional Advanced Nasopharyngeal Carcinoma

Purpose: This retrospective study investigated the effects of cognitive behavioral therapy (CBT) on depression, anxiety, response rates, and adverse events in patients with locoregional advanced nasopharyngeal carcinoma (NPC). Methods: A total of 269 patients with diagnosis of stage III-IVA NPC received either CBT plus chemoradiotherapy (CBT group, n = 136) or treatment as usual (TAU) plus chemoradiotherapy (TAU group, n = 133). Patients in the CBT group received a series of 6 CBT sessions for 6 weeks during concurrent chemoradiotherapy. Depression and anxiety were assessed using the Hospital Anxiety and Depression Scale (HADS) score at baseline, the completion of radiotherapy, and 6, 12, and 24 months after radiotherapy. Response rates and adverse events were also evaluated. Results: Patients in the CBT group showed significantly less depression and anxiety than patients in the TAU group after the completion of radiotherapy ( P < .05). Complete response rates were 99.3% (135/136) and 92.5% (123/133) in the CBT group and TAU group with a small effect size (Phi coefficient = .171), respectively ( P = .005). Compared with the TAU group, the CBT group showed a significantly lower incidence of acute adverse events and late toxic effects. Conclusions: The addition of CBT to chemoradiotherapy significantly reduced depressive and anxiety symptoms. CBT combined with chemoradiotherapy is associated with improved response rates, with reduced incidence of toxic effects in patients with locoregional advanced NPC. Based on this study, we registered a randomized controlled clinical trials to better define the role of CBT in patients with locoregional advanced NPC (Registration number: ChiCTR2000034701).

Treating Alpelisib-Induced Hyperglycemia with Very Low Carbohydrate Diets and Sodium-Glucose Co-Transporter 2 Inhibitors: A Case Series

Alpelisib is a α-selective phosphatidylinositol 3-kinase (PI3K) inhibitor approved for treatment of postmenopausal women, and men, with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2–), PIK3CA-mutated, advanced breast cancer (ABC). Hyperglycemia is a common, on-target adverse effect that impairs treatment efficacy and increases the rate of treatment delays, dose reductions, and discontinuation. Currently, there are no clear guidelines on how to manage hyperglycemia due to alpelisib when metformin is not effective. In this case series, we review 3 subjects with ABC that developed hyperglycemia during alpelisib-fulvestrant therapy and were successfully managed with dietary and pharmacologic interventions. These cases provide anecdotal evidence to support the use of sodium-glucose co-transporter-2 inhibitors (SGLT2i) and very low carbohydrate diets to minimize hyperglycemia during alpelisib therapy.

Huaier Inhibits Proliferation, Migration, and Invasion of Cutaneous Squamous Cell Carcinoma Cells by Inhibiting the Methylation Levels of CDKN2A and TP53

Cutaneous squamous cell carcinoma (CSCC) is a malignant tumor that originates from keratinocytes in the epidermis or appendage. Traditional Chinese medicine Huaier has anti-tumor activity in various malignancies. Little is known about the role of Huaier in CSCC. Here, we investigated the function of Huaier in CSCC. We treated CSCC cell line (SCL-1 and A431) with a series of concentration gradients of Huaier to examine the half maximal inhibitory concentration (IC50) of Huaier on SCL-1 and A431 cells. The IC50 of Huaier on growth of SCL-1 and A431 cells were 6.96 and 7.57 mg/mL, respectively. Moreover, Huaier reduced the methylation levels of CDKN2A and TP53, and enhanced the expression of CDKN2A and TP53 in SCL-1 and A431 cells in a dosage-dependent manner. The expression of DNA methyltransferase DNMT1 was severely repressed by Huaier treatment in SCL-1 and A431 cells. DNMT1 overexpression enhanced the methylation levels of CDKN2A and TP53, and suppressed the expression of CDKN2A and TP53 in Huaier-treated SCL-1 and A431 cells. Huaier treatment inhibited proliferation, migration, and invasion of SCL-1 and A431 cells. However, inhibition of CDKN2A or TP53 reversed the influence of Huaier treatment on proliferation, migration, and invasion of CSCC cells. In conclusion, our data demonstrate that Huaier inhibits proliferation, migration, and invasion of CSCC cells by regulating DNA methylation of CDKN2A and TP53, thereby attenuating the progression of CSCC. Thus, Huaier extract may act as a drug for treating CSCC.