Phytocompounds-based therapeutic approach: Investigating curcumin and green tea extracts on MCF-7 breast cancer cell line.

BACKGROUND: Breast cancer (BC) has transcended lung cancer as the most common cancer in the world. Due to the disease's aggressiveness, rapid growth, and heterogeneity, it is crucial to investigate different therapeutic approaches for treatment. According to the World Health Organization (WHO), Plant-based therapeutics continue to be utilized as safe/non-toxic complementary or alternative treatments for cancer, even in developed countries, regardless of how cutting-edge conventional therapies are. Despite their low bioavailability, curcumin (CUR) and green tea (GT) represent safer therapeutic options. Due to their potent molecular-modulating properties on various cancer-related molecules and signaling pathways, they are considered gold-standard therapeutic agents and have been incorporated into the development of one or more therapeutic strategies of BC treatment. METHODS: We investigated the modulatory role of CUR and GT extracts on significant multi molecular targets in MCF-7 BC cell line to assess their potential as BC multi-targeting agents. We analyzed the phytocompounds in GT leaves using High-performance liquid chromatography (HPLC) and Gas chromatography-mass spectrometry (GC-MS) techniques. The mRNA expression levels of Raf-1, Telomerase, Tumor necrosis factor alpha (TNF-α) and Interleukin-8 (IL-8) genes in MCF-7 cells were quantified using quantitative real-time PCR (qRT-PCR). The cytotoxicity of the extracts was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the released Lactate dehydrogenase (LDH), a valuable marker for identifying the programmed necrosis (necroptosis). Additionally, the concentrations of the necroptosis-related proinflammatory cytokines (TNF-α and IL-8) were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: In contrast to the GT, the results showed the anticancer and cytotoxic properties of CUR against MCF-7 cells, with a relatively higher level of released LDH. The CUR extract downregulated the oncogenic Raf-1, suppressed the Telomerase and upregulated the TNF-α and IL-8 genes. Results from the ELISA showed a notable increase in IL-8 and TNF-α cytokines levels after CUR treatment, which culminated after 72 h. CONCLUSIONS: Among both extracts, only CUR effectively modulated the understudy molecular targets, achieving multi-targeting anticancer activity against MCF-7 cells. Moreover, the applied dosage significantly increased levels of the proinflammatory cytokines, which represent a component of the cytokines-targeting-based therapeutic strategy. However, further investigations are recommended to validate this therapeutic approach.

Caregiver burden among family caregivers of incurable cancer patients in two eastern Mediterranean countries.

BACKGROUND: Although family caregivers (FCs) play an important role in the care provided to incurable cancer patients in our region, little is known about the burden they experience. This study was conducted to determine the prevalence of caregiver burden (CB) among FCs of incurable cancer patients in two Eastern Mediterranean countries and to identify factors that may be associated with significant CB. METHODS: The study included 218 FCs, 165 from Egypt and 53 from Saudi Arabia. The 22-item Zarit Burden Interview (ZBI-22) was used to assess caregiver burden CB. Significant CB was defined as a ZBI-22 score ≥ 21. The assistance with basic ADLs was classified into 3 levels according to FCs' assistance with early/middle/late-loss basic ADLs. The relationship between CB and the assistance with ADLs and other factors was studied. RESULTS: The mean (SD) ZBI-22 score among FCs was 23.4 (9.3) and the majority (128/218, 59%) had significant CB. Eighty-nine percent of FCs assisted with at least one basic ADL. Assistance with late-loss basic ADLs, best supportive care treatment plan and poorer performance status were associated with higher CB (p < 0.0001, =0.018 and = 0.005). However, in logistic regression analysis, only assistance with late-loss ADLs was independently associated with significant CB (OR = 3.4 [95%CI:1.2-9.7], p = 0.024). CONCLUSION: A substantial proportion of FCs of incurable cancer patients in our region experience significant CB. Family caregivers assisting with late-loss basic ADLs are at risk of significant CB and should be routinely screened for CB.

Evaluation of target volume margins for radiotherapy of prostate implanted with fiducial markers.

The planning target volume (PTV) depends on the method of radiotherapy guidance. This study aimed to measure the systemic and random errors using an online marker matching and offline bone structure matching to estimate PTVmarker, PTVbone, or PTVlaser for treatment verification and radiotherapy guidance, especially in centers lacking radiotherapy fiducial markers (FMs). Thirty patients with localized prostate cancer who were treated with FM-based dose escalation protocol were included. The initial set-up was done with laser marks and daily megavoltage images were acquired. The systematic and random errors were calculated. PTVmarker, defined as the sum of maximum marker migration, and PTV calculated to compensate for the difference between online marker matching and offline analysis of marker matching. PTVmarker was added to estimated PTV from online marker matching to obtain PTVlaser. PTVskin marks migration, was calculated and deducted from PTVlaser to acquire PTVbone. The mean maximum marker migration was 2 ± 1.2 mm. The resultant values of PTVmarker were 2.7 ± 0.6 mm, 3.3 ± 1.1 mm, and 4.4 ± 2.2 mm, in the lateral (lat.), longitudinal (long) & vertical (vert.) directions, respectively, whereas values of PTVlaser were 13 ± 0.6 mm, 17.7 ± 1.1 mm, and 15.8 ± 2.2 mm, and PTVbone were 5.9 ± 0.6 mm, 8.6 ± 1.1 mm, 7.2 ± 2.2 mm, respectively, in the lat., long., and vert. directions. Our results show that PTV needed with FM-based image guidance ranged between 3 and 4 mm in the three cardinal directions, was 10 mm smaller than that required with laser skin marks guidance, and narrower by 5 mm compared to that obtained by offline bone structure image matching.

Addition of 3-day aprepitant to ondansetron and dexamethasone for prophylaxis of chemotherapy-induced nausea and vomiting among patients with diffuse large B cell lymphoma receiving 5-day cisplatin-based chemotherapy.

BACKGROUND: Neurokinin-1 receptor antagonists, such as aprepitant are currently emerging as powerful prophylactic agents for chemotherapy-induced nausea and vomiting (CINV). Therefore, it is important to adjust the anti-emetic regimens based on personal risk factors of the patient, duration of the chemotherapy regimen and cost-effectiveness. PURPOSE: To determine the efficacy of the 3-day aprepitant along with ondansetron and dexamethasone in controlling CINV in patients with large B cell lymphoma receiving multiday-cisplatin regimen chemotherapy. METHODS: This is a pilot prospective cross-over trial. Patients were allocated to either aprepitant 125mg on day 1 and 80mg on days 2 & 3 or placebo in the first 2 cycles, with crossover to the opposite treatment in the 3rd and 4th cycles. The primary end point was complete response (CR) of both acute (days 1-5) and delayed (days 6-8) CINV. CR means neither to develop emetic episodes nor to use rescue anti-emetics medication. RESULTS: Twelve of the 15 patients recruited for the study were fully evaluable and completed 4 cycles of ESHAP regimen with a total of 48 cycles given. In the cycles with aprepitant and those without the CR were 83.3% and 0% respectively (p<0.05). Patients receiving aprepitant in the first 2 cycles recorded less nausea in subsequent cycles that were given without aprepitant. This was not statistically significant. CONCLUSION: This triple anti-emetic regimen showed efficacy in controlling the multi-day cisplatin-induced nausea and vomiting. Further randomized controlled trials are needed to compare between 3-day and 7-day aprepitant for multi-day cisplatin regimens.

The fear of using tramadol for pain control (tramadolophobia) among Egyptian patients with cancer.

OBJECTIVES: The fear of using tramadol for pain control (tramadolophobia) by Egyptian patients with cancer is a frequent problem in our practice. This study was conducted to explore the prevalence of and the reasons behind tramadolophobia among Egyptian patients with cancer. METHODS: A structured interview including open-ended and closed questions. The study included 178 adult patients with cancer from two cancer centers in Cairo and Sharkia, Egypt. RESULTS: The source of information about tramadol was a non-healthcare-related source in 168 (94 percent) patients, mainly the media (50 percent). The believed uses of tramadol were abuse related in 94 (53 percent) patients, stimulant (physical, sexual, and to boost alertness) in 59 (33 percent), and analgesic in 55 (31 percent). Twenty-six (15 percent) patients gave history of tramadol use, largely (69 percent) as a stimulant. In case tramadol was prescribed for pain control, 90 (51 percent) patients refused to take it, 59 (33 percent) patients agreed to take it with concern about addiction, and only 29 (16 percent) patients agreed without concerns. Among those who refused taking tramadol for pain, the mentioned reason of refusal was addiction-related fears in 57 percent. CONCLUSIONS: The stigmatization and misconceptions about tramadol may have resulted in tramadolophobia among the majority of Egyptian patients with cancer. This further complicates the barriers to cancer pain control in Egypt. Being the only available World Health Organization step-II analgesic in Egypt, interventions to overcome tramadolophobia should be taken.