Critical role of Aquaporin-1 and telocytes in infantile hemangioma response to propranolol beta blockade.

Propranolol, a nonselective ß-adrenergic receptor (ADRB) antagonist, is the first-line therapy for severe infantile hemangiomas (IH). Since the incidental discovery of propranolol efficacy in IH, preclinical and clinical investigations have shown evidence of adjuvant propranolol response in some malignant tumors. However, the mechanism for propranolol antitumor effect is still largely unknown, owing to the absence of a tumor model responsive to propranolol at nontoxic concentrations. Immunodeficient mice engrafted with different human tumor cell lines were treated with anti-VEGF bevacizumab to create a model sensitive to propranolol. Proteomics analysis was used to reveal propranolol-mediated protein alteration correlating with tumor growth inhibition, and Aquaporin-1 (AQP1), a water channel modulated in tumor cell migration and invasion, was identified. IH tissues and cells were then functionally investigated. Our functional protein association networks analysis and knockdown of ADRB2 and AQP1 indicated that propranolol treatment and AQP1 down-regulation trigger the same pathway, suggesting that AQP1 is a major driver of beta-blocker antitumor response. Examining AQP1 in human hemangioma samples, we found it exclusively in a perivascular layer, so far unrecognized in IH, made of telocytes (TCs). Functional in vitro studies showed that AQP1-positive TCs play a critical role in IH response to propranolol and that modulation of AQP1 in IH-TC by propranolol or shAQP1 decreases capillary-like tube formation in a Matrigel-based angiogenesis assay. We conclude that IH sensitivity to propranolol may rely, at least in part, on a cross talk between lesional vascular cells and stromal TCs.

Xenopus: An in vivo model for studying skin response to ultraviolet B irradiation.

Ultraviolet B (UVB) in sunlight cause skin damage, ranging from wrinkles to photoaging and skin cancer. UVB can affect genomic DNA by creating cyclobutane pyrimidine dimers (CPDs) and pyrimidine-pyrimidine (6-4) photoproducts (6-4PPs). These lesions are mainly repaired by the nucleotide excision repair (NER) system and by photolyase enzymes that are activated by blue light. Our main goal was to validate the use of Xenopus laevis as an in vivo model system for investigating the impact of UVB on skin physiology. The mRNA expression levels of xpc and six other genes of the NER system and CPD/6-4PP photolyases were found at all stages of embryonic development and in all adult tissues tested. When examining Xenopus embryos at different time points after UVB irradiation, we observed a gradual decrease in CPD levels and an increased number of apoptotic cells, together with an epidermal thickening and an increased dendricity of melanocytes. We observed a quick removal of CPDs when embryos are exposed to blue light versus in the dark, confirming the efficient activation of photolyases. A decrease in the number of apoptotic cells and an accelerated return to normal proliferation rate was noted in blue light-exposed embryos compared with their control counterparts. Overall, a gradual decrease in CPD levels, detection of apoptotic cells, thickening of epidermis, and increased dendricity of melanocytes, emulate human skin responses to UVB and support Xenopus as an appropriate and alternative model for such studies.

Does saffron supplementation have favorable effects on liver function indicators? A systematic review and meta-analysis of randomized controlled trials.

Several pharmaceutical and non-pharmaceutical approaches have been suggested to improve liver health. There is a large discrepancy in the effects of saffron supplementation on liver function in adults. To fill this knowledge gap, this systematic review and meta-analysis of randomized controlled trials (RCTs) assess the effects of saffron supplementation on liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). A systematic search current to August 2020 was performed in PubMed/Medline, Scopus, Web of Science, and Google Scholar using relevant keywords to detect eligible articles. A random-effects model was used to estimate the weighted mean difference (WMD) and 95% confidence (95% CI). Nine eligible trials were included in the final analysis. The pooled analysis revealed that serum ALT concentrations were significantly reduced using saffron compared to placebo (WMD: -2.39 U/L; 95% CI: -4.57 to -0.22; P = 0.03, I2= 87.9%, P < 0.001). However, saffron supplementation did not affect levels of serum AST (WMD: 1.12 U/L; 95% CI: -1.42 to 3.65; P = 0.39) or ALP (WMD: 4.32 U/L; 95% CI: -6.91 to 15.54; P = 0.78). In the dose-response analysis, we did not find a significant dose-response relationship between dosage and duration of saffron supplementation on serum levels of ALT, AST, and ALP. We found that saffron supplementation can reduce ALT serum concentrations without significant effects on other liver function indicators, including AST and ALP. Nevertheless, future large RCTs on diverse populations are needed to understand better the effects of saffron and its constituents on these enzymes.

Does Ashwagandha supplementation have a beneficial effect on the management of anxiety and stress? A systematic review and meta-analysis of randomized controlled trials.

Clinical trial studies revealed conflicting results on the effect of Ashwagandha extract on anxiety and stress. Therefore, we aimed to evaluate the effect of Ashwagandha supplementation on anxiety as well as stress. A systematic search was performed in PubMed/Medline, Scopus, and Google Scholar from inception until December 2021. We included randomized clinical trials (RCTs) that investigate the effect of Ashwagandha extract on anxiety and stress. The overall effect size was pooled by random-effects model and the standardized mean difference (SMD) and 95% confidence interval (CIs) for outcomes were applied. Overall, 12 eligible papers with a total sample size of 1,002 participants and age range between 25 and 48 years were included in the current systematic review and meta-analysis. We found that Ashwagandha supplementation significantly reduced anxiety (SMD: -1.55, 95% CI: -2.37, -0.74; p = .005; I2  = 93.8%) and stress level (SMD: -1.75; 95% CI: -2.29, -1.22; p = .005; I2  = 83.1%) compared to the placebo. Additionally, the non-linear dose-response analysis indicated a favorable effect of Ashwagandha supplementation on anxiety until 12,000 mg/d and stress at dose of 300-600 mg/d. Finally, we identified that the certainty of the evidence was low for both outcomes. The current systematic review and dose-response meta-analysis of RCTs revealed a beneficial effect in both stress and anxiety following Ashwagandha supplementation. However, further high-quality studies are needed to firmly establish the clinical efficacy of the plant.

The Effect of Early Mobilization on Respiratory Parameters of Mechanically Ventilated Patients With Respiratory Failure.

The effect of early mobilization on hemodynamic parameters of patients under mechanical ventilation has been associated with positive results and yet its effect on specific respiratory parameters is less well appreciated. This article reports the results of a study of a randomized clinical trial of intensive care unit patients receiving mechanical ventilation. The findings of this study confirmed that a 4-step protocol for early mobilization can improve Pao2, O2 saturation, Pao2/Fio2 (fraction of inspired oxygen) ratio, and pulmonary compliance. The value of interdisciplinary collaboration supporting early mobilization was confirmed.

Is Infantile Hemangioma a Neuroendocrine Tumor?

Infantile hemangioma (IH) is the most common infantile tumor, affecting 5-10% of newborns. Propranolol, a nonselective ß-adrenergic receptor (ADRB) antagonist, is currently the first-line treatment for severe IH; however, both its mechanism of action and its main cellular target remain poorly understood. Since betablockers can antagonize the effect of natural ADRB agonists, we postulated that the catecholamine produced in situ in IH may have a role in the propranolol response. By quantifying catecholamines in the IH tissues, we found a higher amount of noradrenaline (NA) in untreated proliferative IHs than in involuted IHs or propranolol-treated IHs. We further found that the first three enzymes of the catecholamine biosynthesis pathway are expressed by IH cells and that their levels are reduced in propranolol-treated tumors. To study the role of NA in the pathophysiology of IH and its response to propranolol, we performed an in vitro angiogenesis assay in which IH-derived endothelial cells, pericytes and/or telocytes were incorporated. The results showed that the total tube formation is sensitive to propranolol only when exogenous NA is added in the three-cell model. We conclude that the IH's sensitivity to propranolol depends on crosstalk between the endothelial cells, pericytes and telocytes in the context of a high local amount of local NA.

Post-Marketing Surveillance of a generic Oxaliplatin (AlvoxalⓇ) in Iranian Patients with Cancer.

BACKGROUND: CRC is the second and third most common cancer in women and men, respectively. The national comprehensive cancer network guidelines recommend oxaliplatin-based chemotherapy as a preferred regimen for patients with advanced or metastatic colon cancer. Oxaliplatin is also used in the off-label treatment of gastric cancer. FDA uses post-marketing study commitments to gather additional information about a product's safety, efficacy, or optimal use. It is necessary to perform safety monitoring after marketing authorization is received; such monitoring can be done by means of characterizing the safety of drugs in patients being treated in real-world clinical practice settings. OBJECTIVES: This Phase IV study aimed to evaluate the safety profile of a brand-name formulation of the generic drug oxaliplatin (AlvoxalⓇ, NanoAlvand, Tehran, Iran) in Iranian patients diagnosed with either colorectal or other, different types of cancer. METHODS: Patients with colorectal cancer, gastric cancer, or other malignancies receiving oxaliplatin as a part of their treatment were included in this open-label, multicenter, observational Phase IV study. This study aimed to assess the safety profile of oxaliplatin in patients diagnosed with different cancers. FINDINGS: A total of 483 patients from 16 cities in Iran were enrolled. The most common malignancy was colorectal cancer (55.49%), followed by gastric cancer (28.16%). Based on the results, 405 patients experienced at least 1 adverse event. Most of these adverse events were grade 1 or 2, and the most commonly reported adverse event was anemia (60.66%). During the study, 26 serious adverse events occurred in 15 (3.11%) patients, which were perhaps related to oxaliplatin. There were no remarkable differences in the incidences of adverse events in the system organ classes of blood and lymphatic system disorders, gastrointestinal disorders, or nervous system disorders among patients with different malignancies (ie, colorectal cancer, gastric cancer, and other malignancies) or between genders. The results of this open-label, multicenter, observational, postmarketing surveillance study demonstrated no unexpected safety findings from the use of this oxaliplatin product (AlvoxalⓇ) in Iranian patients diagnosed with different types of cancer. CONCLUSIONS: This Phase IV study provides data on the safety profile of a number of chemotherapy regimens containing an oxaliplatin product given to Iranian patients diagnosed with different types of cancer.

The effect of Alpha-lipoic acid supplementation on endothelial function: A systematic review and meta-analysis.

There is evidence that alpha-lipoic acid (ALA) supplementation plays an important role in preventing cardiovascular diseases. However, its effect, specifically, on endothelial function (EF) is unclear. Therefore, this systematic review and meta-analysis aimed to evaluate the effects of ALA supplementation on EF. Databases including PubMed/Medline, Scopus, and ISI Web of Science were searched to identify eligible publications from inception up to April 2020. Randomized controlled trials assessing the effect of ALA supplementation on flow-mediated dilation (FMD) levels in adults were included. The pooled results were obtained using the random-effects model and are expressed as weighted mean differences (WMD) with 95% confidence intervals (CI). Five studies including six effect sizes and 300 participants were included. ALA supplementation significantly increased FMD levels by 2.36% (95% CI: 1.21-3.51; p < .001), compared with the control. Subgroup analyses suggested that the effects of ALA on FMD could be changed by age and health status of the participants. Dose-response analysis also showed that ALA dosage had a significant non-linear effect on FMD levels. The results showed that ALA supplementation appears to improve the EF. However, the role of ALA supplementation in improving other biomarkers of EF requires further research.

Leukemia inhibitory factor signaling in Xenopus embryo: Insights from gain of function analysis and dominant negative mutant of the receptor.

Leukemia inhibitory factor (LIF) is a cytokine member of the interleukin 6 family (IL6) of cytokines. It signals through a heterodimer receptor complex that consists of the LIF receptor (or LIFR formerly known as gp190) and the Interleukin 6 signal transducer (or IL6ST formerly known as gp130). LIF signaling is mediated mainly by signal transducer and activator of transcription 3 (STAT3) and has a wide variety of biological activities with pleiotropic effects on many cell types and organs among which are stem cell renewal and implantation process in mammalian embryo. Despite the wealth of data on LIF in mammalian cells, there is a paucity of information on its functions in lower vertebrates. Here, we provide information on the status and the function of LIF signaling in Xenopus amphibian. The IL6 cytokine family is highly conserved in Xenopus genome both at ligands and receptors levels. All cytokines and receptors of the family, except oncostatin M (OSM) and IL27, can be identified in the genome including the orthologs of LIF, cardiotrophin 1 (CTF1), ciliary neurotrophic factor (CNTF), cardiotrophin like cytokine factor 1 (CLCF1), LIFR, IL6ST, IL6R, IL11RA and CNTFR. Lif mRNA is zygotically expressed after midblastula transition while lifr and il6st are maternally expressed. We have investigated the functions of LIF in Xenopus early development with a gain-of-function analysis combined to the use of a dominant negative form of the receptor. The overexpression of Xenopus lif in embryo activates STAT3 phosphorylation and induces a dramatic phenotype where embryos are ventralised and show a reduction of anterior structures with microcephaly. This results mainly from BMP signal stimulation and antagonism towards IGF signals. In addition, most embryos develop tumor-like cell masses according to both autonomous and non-autonomous processes. Through the use of a dominant negative form of the receptor, we demonstrate for the first time that a functional LIF signaling is required for normal vertebrate kidney development. Owing to its experimental advantages, the Xenopus embryo constitutes a useful model to identify the molecular actors that may account for the pleiotropic functions of LIF and their role in vertebrate development.

Energy metabolism in skin cancers: A therapeutic perspective.

Skin cancers are the most common cancers worldwide. The incidence of common skin cancers, including basal cell carcinomas (BCCs), squamous cell carcinomas (SCCs) and melanomas, continues to rise by 5 to 7% per year, mainly due to ultraviolet (UV) exposure and partly because of aging. This suggests an urgent necessity to improve the level of prevention and protection for skin cancers as well as developing new prognostic and diagnostic markers of skin cancers. Moreover, despite innovative therapies especially in the fields of melanoma and carcinomas, new therapeutic options are needed to bypass resistance to targeted therapies or treatment's side effects. Since reprogramming of cellular metabolism is now considered as a hallmark of cancer, some of the recent findings on the role of energy metabolism in skin cancer initiation and progression as well as its effect on the response to targeted therapies are discussed in this review. This article is part of a Special Issue entitled Mitochondria in cancer, edited by Giuseppe Gasparre, Rodrigue Rossignol and Pierre Sonveaux.

A new eco-friendly and water-resistant sunscreen agent: Lecithin-based multilamellar liposomes.

BACKGROUND: UV skin exposure is an important matter of public health, as the worldwide rising prevalence of skin cancers indicates. However, a wide majority of commercially available sunscreens are responsible for ocean ecosystem damages such as coral reef degradation and phytoplankton mortality. AIMS: To answer the urge for new eco-friendly UV filters, we studied the use of lecithin-based multilamellar liposomes (MLLs) of controlled size and elasticity as a bio-sourced and biodegradable alternative to classic sunscreens. These parameters control allows different skin layers targeting. METHODS: The performance of two different MLLs compositions and a commercially available SPF50+ water-resistant liposomal sunscreen was compared on skin explants. SC-MLLs target the stratum corneum and Epi-MLLs the whole epidermis. Preparations were applied prior to skin irradiation. Their efficiencies were evaluated histologically (hematoxylin and eosin staining plus cyclobutane pyrimidine dimer [CPD] immunostaining) and by skin barrier quality assessment (trans-epithelial electrical resistance). Adhesiveness to the skin was also investigated. RESULTS: Altogether, ex vivo results indicate MLLs offer a solar protection as effective as a SPF50+ water-resistant liposomal sunscreen but with a better skin adhesiveness and an improved skin barrier function. CONCLUSION: Lecithin-based MLLs of controlled physicochemical parameters can be used as a new eco-friendly and water-resistant agent for solar protection. The stratum corneum targeted action of SC-MLLs appears to be more interesting, as SC-MLLs exhibit an overall better performance than Epi-MLLs at a lower cost. The skin barrier improvement showcased could be of interest to people suffering from dry skin or skin barrier impairment related disease.

Investigation of Fibroblast Growth Factor Peptide Antagonist on Mouse Model Breast Tumor through ERK/MAPK and PI3K/AKT Signaling Pathways.

BACKGROUND: In the majority of cancers, metastasis of tumor cells is the main cause of treatment failure. This study intended to investigate the effectiveness of basic fibroblast growth factor (bFGF) peptide designed to inhibit tumor growth in 4T1 metastatic breast cancer through the PI3K/AKT and ERK/MAPK signal transduction pathways. METHODS: The tumor was induced through 4T1 tumor graft in BALB/c mice. The designed peptide was injected intraperitoneal at three selected doses after two weeks for 14 days. The PBS and doxorubicin were used as the negative and positive control groups, respectively. Tumor size was measured and after the treatment period, the mice underwent a surgery and tumors were used for the western blot examinations. RESULTS: the peptide injection was effective in reducing or inhibiting tumor growth in mice model and in vitro. The western blot analysis results showed that the p-AKT and p-ERK levels in peptide treated tumors were reduced (p<0.05). CONCLUSION: The peptide injection was effective in mice model. Findings showed that in the two signal transduction pathways, the p-AKT and p-ERK levels were significantly different from the negative control group.

Delving into the Metabolism of Sézary Cells: A Brief Review.

Primary cutaneous lymphomas (PCLs) are a heterogeneous group of lymphoproliferative disorders caused by the accumulation of neoplastic T or B lymphocytes in the skin. Sézary syndrome (SS) is an aggressive and rare form of cutaneous T cell lymphoma (CTCL) characterized by an erythroderma and the presence of atypical cerebriform T cells named Sézary cells in skin and blood. Most of the available treatments for SS are not curative, which means there is an urgent need for the development of novel efficient therapies. Recently, targeting cancer metabolism has emerged as a promising strategy for cancer therapy. This is due to the accumulating evidence that metabolic reprogramming highly contributes to tumor progression. Genes play a pivotal role in regulating metabolic processes, and alterations in these genes can disrupt the delicate balance of metabolic pathways, potentially contributing to cancer development. In this review, we discuss the importance of targeting energy metabolism in tumors and the currently available data on the metabolism of Sézary cells, paving the way for potential new therapeutic approaches aiming to improve clinical outcomes for patients suffering from SS.

Bing-Neel syndrome, a rare manifestation of WM; a case report and review of literature.

Bing-Neel syndrome (BNS) is a rare manifestation in individuals suffering from Waldenström macroglobulinemia (WM). Neurological signs and symptoms in this syndrome are almost difficult to be differentiated from other common neurological manifestations of hyper-viscosity or Waldenström-associated polyneuropathy. In this paper, we report a new case of WM with concurrent BNS, then review the clinical picture and treatment of this syndrome.

Xenopus as a model system for studying pigmentation and pigmentary disorders.

Human pigmentary disorders encompass a broad spectrum of phenotypic changes arising from disruptions in various stages of melanocyte formation, the melanogenesis process, or the transfer of pigment from melanocytes to keratinocytes. A large number of pigmentation genes associated with pigmentary disorders have been identified, many of them awaiting in vivo confirmation. A more comprehensive understanding of the molecular basis of pigmentary disorders requires a vertebrate animal model where changes in pigmentation are easily observable in vivo and can be combined to genomic modifications and gain/loss-of-function tools. Here we present the amphibian Xenopus with its unique features that fulfill these requirements. Changes in pigmentation are particularly easy to score in Xenopus embryos, allowing whole-organism based phenotypic screening. The development and behavior of Xenopus melanocytes closely mimic those observed in mammals. Interestingly, both Xenopus and mammalian skins exhibit comparable reactions to ultraviolet radiation. This review highlights how Xenopus constitutes an alternative and complementary model to the more commonly used mouse and zebrafish, contributing to the advancement of knowledge in melanocyte cell biology and related diseases.

The effect of conjugated linoleic acid supplementation in comparison with omega-6 and omega-9 on lipid profile: a graded, dose-response systematic review and meta-analysis of randomized controlled trials.

Conjugated linoleic acid (CLA) is a geometrical isomer of linoleic acid, which has anti-inflammatory, anti-diabetic, anti-cancer, and anti-obesity properties. However, the studies reported inconstant results about the CLA-related effects on lipid profiles. As a result, meta-analysis and systematic review were performed to survey the CLA supplementation-related effect on lipid profile including high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol (TC), and triglycerides (TG). To identify the relevant research, a systematic comprehensive search was initiated on the medical databases such as Scopus and PubMed/Medline until December 2022. The overall effect size was estimated by weighted mean difference (WMD) and 95% confidence interval (CI) in a random effect meta-analysis. In the final quantitative analysis, the meta-analysis considered 35 randomized controlled trials (RCTs) with 1,476 participants (707 controls and 769 cases). The pooled results demonstrated that CLA supplementation, compared with olive oil, significantly increased serum TG levels (WMD: 0.05 mmol/L; 95% CI: 0.01 to 0.1; p = 0.04; I2 = 0.0%, p = 0.91). With regard to TC level, CLA supplementation compared with placebo significantly reduced TC concentrations (WMD: -0.08 mmol/L; 95% CI: -0.14 to -0.02; p < 0.001; I2 = 82.4%). Moreover, the non-linear dose-response analysis indicated a decreasing trend of TC serum level from the 15th week of CLA supplementation compared with olive oil (Pnon-linearity = 0.01). The present meta-analysis and systematic review of 35 RCTs showed that the CLA intervention was able to raise the level of TG in comparison to olive oil; however, it can decrease TC level compared with placebo and olive oil.

Loss of epidermal hypoxia-inducible factor-1α accelerates epidermal aging and affects re-epithelialization in human and mouse.

In mouse and human skin, HIF-1α is constitutively expressed in the epidermis, mainly in the basal layer. HIF-1α has been shown to have crucial systemic functions: regulation of kidney erythropoietin production in mice with constitutive HIF-1α epidermal deletion, and hypervascularity following epidermal HIF-1α overexpression. However, its local role in keratinocyte physiology has not been clearly defined. To address the function of HIF-1α in the epidermis, we used the mouse model of HIF-1α knockout targeted to keratinocytes (K14-Cre/Hif1a(flox/flox)). These mice had a delayed skin phenotype characterized by skin atrophy and pruritic inflammation, partly mediated by basement membrane disturbances involving laminin-332 (Ln-332) and integrins. We also investigated the relevance of results of studies in mice to human skin using reconstructed epidermis and showed that HIF-1α knockdown in human keratinocytes impairs the formation of a viable reconstructed epidermis. A diminution of keratinocyte growth potential, following HIF-1α silencing, was associated with a decreased expression of Ln-322 and α6 integrin and ß1 integrin. Overall, these results indicate a role of HIF-1α in skin homeostasis especially during epidermal aging.

Retroperitoneal lymphangioma as the final diagnosis of a middle-aged woman with abdominal pain: a case report.

BACKGROUND: Lymphangiomas are lesions attributed to congenital malformations of the lymphatic system, or acquired chronic obstruction of the lymphatic network due to trauma, radiation, surgical manipulation, inflammation, or infection. Overall, lymaphangiomas are rare, and particularly, retroperitoneal lymphangiomas are far more uncommon per reported cases. CASE PRESENTATION: A 49-year-old Iranian woman presented with a progressive abdominal pain since approximately 1 month before admission. She was found to have a retroperitoneal lymphangioma after a precise radiological and surgical workup. CONCLUSION: Retroperitoneal lymphangiomas are rare lesions, sometimes indistinguishable from malignant lesions originating from pancreas and adjacent organs. Complete surgical removal and histologic evaluation of the lesion is the gold standard of treatment and diagnosis.

Maintenance therapy with Everolimus in patients with refractory or relapsing Hodgkin lymphoma after autologous stem cell transplantation.

Introduction: Patients with relapsing or primary refractory Hodgkin lymphoma, still have unsatisfactory outcomes after high dose chemotherapy followed by autologous stem cell transplantation (ASCT). Brentuximab Vedotin (BV) is the only approved agent for maintenance therapy for up to one year in these patients, however, this agent is often not available or affordable for many patients, especially in the developing countries. In this study, we used Everolimus as maintenance therapy after ASCT among patients with relapsing/refractory Hodgkin lymphoma. Materials and Methods: We collected the data of 20 patients with primary refractory or relapsing Hodgkin lymphoma who had undergone ASCT between June 2016 and June 2021. Everolimus was started at 10 mg daily on day +90 after ASCT for at least two years in patients with stable disease status, confirmed by imaging modalities. Patients were followed for disease status and drug side effects every 3 months. Results: In our single-arm case-series study, the median duration of treatment was 22.95 months. Except for three patients, who had progression, others had no progression and are still receiving Everolimus (85%). No serious side effect was seen. We had no mortality due to disease recurrence. Conclusion: Until now, results showed promising effects of Everolimus in patients with relapsing or primary refractory Hodgkin lymphoma as maintenance therapy after ASCT.

Neoadjuvant chemotherapy outcome with taxane-based versus non-taxane protocols in gastric cancer.

BACKGROUND: Gastric cancer is the fifth most common cancer worldwide. One of the chemotherapy agents, taxanes is important in increasing patients' survival. The purpose of this study is to assess the efficacy of taxane-based drugs versus non-taxanes in neoadjuvant chemotherapy in non-metastatic gastric adenocarcinoma (GA) in Iranian patients. MATERIALS AND METHODS: In a historical cohort method, 65 patients between 18 and 75 years old who suffered from non-metastatic GA were included. Nineteen and 21 and 25 patients, had undergone DCF (docetaxel, cisplatin, 5fluorouracil) and FLOT (5fluorouracil, leucovorin, oxaliplatin, docetaxel) and FOLFOX6 (oxaliplatin, leucovorin, 5fluorouracil) regimens, respectively, between 2018 and 2021. Survival criteria consisting of progression-free survival (PFS), overall survival (OS), progression rate, and mortality rate were evaluated using the Kaplan-Meier method, in a three-year follow-up period. RESULTS: The majority of patients were male (72.3%), with a median age of 65 years. Most of the patients had lesions with tumor, node, metastasis (TNM) stage IIIb (27.7%) and poor differentiated pathological grade (49.2%). OS time had a significant correlation with the low TNM stage (P = 0.01), well-differentiated pathological grade (P = 0.005), and FLOT vs. FOLFOX protocol (20.3 vs. 12.2 months, respectively. P =0.04). FLOT regimen had significantly better OS survival vs. DCF regimen (20.3 vs. 15.4 months, respectively, P = 0.03). No significant correlation was observed between survival criteria and other factors like gender, age, past medical history, Karnofsky scale, and tumor location in the stomach. The taxane-based arm (sum of DSF and FLOT) had no superiority over the non-taxane arm in survival criteria. CONCLUSION: FLOT protocol, as a taxane-based regimen had better survival compared to FOLFOX protocol in neoadjuvant chemotherapy in gastric non-metastatic adenocarcinoma.