RESUMO

Abstract Background: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique that acts on the activity of the cerebral cortex employing electrical currents. Aim: The objective of this project is to evaluate the effectiveness of rTMS on pain and quality of life in patients with chemotherapy-induced peripheral neuropathic pain. Method: Ten patients with chemotherapy-induced peripheral neuropathic pain received 20 sessions of rTMS, consisting of 15 minutes of treatment repeated 5 times per week for four weeks (10 Hz, 20s, 30 trains with 81% intensity). Patients were evaluated using the Brief pain inventory (BPI) and the Functional Assessment of Cancer Therapy and neurotoxicity (FACT-GOG-NTX 13). Results: There were significant differences in BPI mean severity, interference score and FACT-GOG-NTX 13 (p<0,05). Conclusion: The pilot study results suggest that rTMS is potentially beneficial for the treatment of chemotherapy-induced peripheral neuropathy. rTMS over the M1 had an important reduction in pain severity, interference with daily activities, and quality of life scores. However, results should be taken with caution due to the small sample size, absence of a control group and short period of follow-up.

Resumen Antecedentes: La estimulación magnética transcraneal repetitiva (EMTr) es una técnica no invasiva que actúa sobre la actividad de la corteza cerebral, empleando corrientes eléctricas. Objetivo: El objetivo de este proyecto es evaluar la eficacia de la EMTr sobre el dolor y la calidad de vida en pacientes con dolor neuropático periférico inducido por quimioterapia. Métodos: Diez pacientes con dolor neuropático periférico inducido por quimioterapia recibieron 20 sesiones de EMTr que consistieron en un tratamiento de 15 minutos repetido 5 veces por semana durante cuatro semanas (10 Hz, 20 s, 30 trenes con 81 % de intensidad). Los pacientes fueron evaluados mediante el Inventario Breve de Dolor (BPI) y la Evaluación Funcional de la Terapia del Cáncer y la neurotoxicidad (FACT-GOG-NTX 13). Resultados: Hubo diferencias significativas en la severidad media del dolor del BPI, la puntuación de interferencia y el FACT-GOG-NTX 13 (p<0,05). Conclusión: Los resultados del estudio piloto sugieren que la rTMS es potencialmente beneficiosa para el tratamiento de la neuropatía periférica inducida por la quimioterapia. La rTMS sobre M1 tuvo una reducción importante de la severidad del dolor, la interferencia con las actividades diarias y las puntuaciones de calidad de vida. Sin embargo, los resultados deben tomarse con cautela debido al pequeño tamaño de la muestra, la ausencia de un grupo de control y el corto período de seguimiento.

RESUMO

OBJECTIVE: This meta-analysis aimed to evaluate the efficacy and safety of combining pemetrexed and platinum with or without pembrolizumab for the treatment of advanced non-small-cell lung cancer (NSCLC). METHODS: A systematic search of PubMed, Embase, Cochrane Library, and Web Of Science databases was conducted to identify studies comparing pemetrexed and platinum with or without pembrolizumab in advanced NSCLC. Raw data were extracted from eligible studies to calculate Hazard Ratios (HR) for Progression-Free Survival (PFS) and Overall Survival (OS), as well as rates of adverse events of all grades and those of Grade 3 or higher. RESULTS: Eight studies with 1639 patients occurred advanced NSCLC included. The group receiving pembrolizumab in combination with pemetrexed and platinum showed significant benefits in terms of OS (HR 0.63; 95% CI 0.54-0.73; p < 0.00001) and PFS (HR:0.64; 95% CI 0.48-0.85; p = 0.002) compared to the group receiving pemetrexed and platinum alone. However, this benefit was accompanied by a higher incidence of Grade 3 or higher adverse events (OR: 1.55; 95% CI 1.24-1.95; p = 0.0001). CONCLUSION: The combination of pemetrexed and platinum with pembrolizumab is recommended as a first-line treatment option for advanced NSCLC due to its significant efficacy benefits. However, the increased risk of Grade 3 or higher adverse events suggests the need for careful consideration and assessment when considering this regimen for second-line or subsequent therapy.

RESUMO

Visceral leishmaniasis, caused by Leishmania infantum in New World countries, is the most serious and potentially fatal form of leishmaniasis, if left untreated. There are currently no effective prophylactic measures, and therapeutic options are limited. Therefore, we investigated whether the aromatase inhibitor letrozole (LET), which is already used to treat breast cancer, has an antileishmanial activity and/or immunomodulatory potential and therefore may be used to treat L. infantum infection. LET was active against L. infantum promastigote and amastigote life cycle stages in an in vitro infection model using human THP-1 cell-derived macrophages. In human peripheral blood leukocytes ex vivo, LET reduced the internalized forms of L. infantum by classical monocytes and activated neutrophils. Concomitantly, LET stimulated the production of IL-12/TNF-α and decreased the production of IL-10/TGF-ß by peripheral blood phagocytes, while in T and B cells, it promoted the production of TNF-α/IFN-γ and decreased that of IL-10. In a murine infection model, LET significantly reduced the parasite load in the liver after just 5 days and in the spleen after 15 days. During in vivo treatment with LET, the production of TNF-α/IFN-γ also increased. In addition, the proportion of developing granulomas decreased and that of mature granulomas increased in the liver, while there was no significant change in organ architecture in the spleen. Based on these data, repositioning of LET may be promising for the treatment of visceral leishmaniasis in humans.

RESUMO

PURPOSE: Real-world evidence on locally advanced or metastatic urothelial carcinoma (la/mUC) management in Spain is limited. This study describes patient characteristics, treatment patterns, survival, and health care resource utilization (HCRU) in this population. METHODS/PATIENTS: This retrospective observational study included all adults with a first diagnosis/record of la/mUC (index date) from January 2015 to June 2020 at nine university hospitals in Spain. Data were collected up to December 31, 2020 (end of study), death, or loss to follow-up. Patient characteristics, treatment patterns, median overall survival (OS) and progression-free survival (PFS) from index date (Kaplan-Meier estimates), and disease-specific HCRU were described. RESULTS: Among 829 patients, median age at diagnosis was 71 years; 70.2% had ≥ 1 comorbidity, and 52.5% were eligible for cisplatin. Median follow-up was 12.7 months. Most (84.7%) patients received first-line systemic treatment; of these, 46.9% (n = 329) received second-line and 16.6% (n = 116) received third-line therapy. Chemotherapy was the most common treatment in all lines of therapy, followed by programmed cell death protein 1/ligand 1 inhibitors. Median (95% confidence interval) OS and PFS were 18.8 (17.5-21.5) and 9.9 (8.9-10.5) months, respectively. Most patients required ≥ 1 outpatient visit (71.8%), inpatient admission (56.6%), or emergency department visit (56.5%). CONCLUSIONS: Therapeutic patterns were consistent with Spanish guideline recommendations. Chemotherapy had a role in first-line treatment of la/mUC in Spain during the study period. However, the disease burden remains high, and new first-line treatments recommended in the latest European guidelines should be made available to patients in Spain.

RESUMO

BACKGROUND: Based on the VIALE-A and VIALE-C studies, the Food and Drug Administration approved venetoclax in 2020 in combination with azacitidine or low-dose cytarabine for the treatment of patients with acute myeloid leukemia ineligible for intensive chemotherapy. After the publication of these studies, venetoclax/azacitidine was assumed to be superior to venetoclax/low-dose cytarabine; however, these studies were not designed to demonstrate superiority between these combinations. Therefore, we conducted a systematic review to describe overall survival, complete remission rate, and composite complete remission rate to assess response of these two regimens in patients with newly diagnosed acute myeloid leukemia who are ineligible for intensive chemotherapy. MATERIALS AND METHODS: The PubMed and Web of Science databases were searched for retrospective studies and complete remission, composite complete remission, and overall survival rates were recorded. RESULTS: Only 11 of the 815 publications identified were eligible to be included n this review, ten studies evaluated the venetoclax/azacitidine combination and one study evaluated the venetoclax/low-dose cytarabine combination. The median overall survival for venetoclax/azacitidine was 10.75 months, whereas for venetoclax/low-dose cytarabine the median overall survival had not been reached at the time of publication. Composite complete remission was 63.3 % for venetoclax/azacitidine and 90 % for venetoclax/low-dose cytarabine. Adverse events were similar for both combinations. CONCLUSIONS: A limited number of studies investigating the venetoclax/low-dose cytarabine combination exist. Based on the available data, the superiority of venetoclax/azacitidine over venetoclax/low-dose cytarabine cannot be assumed for all acute myeloid leukemia patients who are ineligible for intensive chemotherapy. Venetoclax/low-dose cytarabine can still be considered as an option for the drug combinations currently under investigation.

RESUMO

The overexpression of ATP-binding cassette (ABC) transporters contributes to the failure of chemotherapies and symbolizes a great challenge in oncology, associated with the adaptation of tumor cells to anticancer drugs such that these transporters become less effective, a mechanism known as multidrug resistance (MDR). The aim of this review is to present the most widely used methodologies for induction and comprehension of in vitro models for detection of multidrug-resistant (MDR) modulators or inhibitors, including biochemical and morphological techniques for chemosensitivity studies. The overexpression of MDR proteins, predominantly, the subfamily glycoprotein-1 (P-gp or ABCB1) multidrug resistance, multidrug resistance-associated protein 1 (MRP1 or ABCCC1), multidrug resistance-associated protein 2 (MRP2 or ABCC2) and cancer resistance protein (ABCG2), in chemotherapy-exposed cancer lines have been established/investigated by several techniques. Amongst these techniques, the most used are (i) colorimetric/fluorescent indirect bioassays, (ii) rhodamine and efflux analysis, (iii) release of 3,30-diethyloxacarbocyanine iodide by fluorescence microscopy and flow cytometry to measure P-gp function and other ABC transporters, (iv) exclusion of calcein-acetoxymethylester, (v) ATPase assays to distinguish types of interaction with ABC transporters, (vi) morphology to detail phenotypic characteristics in transformed cells, (vii) molecular testing of resistance-related proteins (RT-qPCR) and (viii) 2D and 3D models, (ix) organoids, and (x) microfluidic technology. Then, in vitro models for detecting chemotherapy MDR cells to assess innovative therapies to modulate or inhibit tumor cell growth and overcome clinical resistance. It is noteworthy that different therapies including anti-miRNAs, antibody-drug conjugates (to natural products), and epigenetic modifications were also considered as promising alternatives, since currently no anti-MDR therapies are able to improve patient quality of life. Therefore, there is also urgency for new clinical markers of resistance to more reliably reflect in vivo effectiveness of novel antitumor drugs.

RESUMO

BACKGROUND: Neoadjuvant chemotherapy (NAC), traditionally used for locally advanced disease, is now applied for operable disease, particularly to treat aggressive breast cancer (BC). This study aimed to characterize the pathological complete response (pCR) and its relationship with overall survival (OS) and disease-free survival (DFS) among BC patients receiving NAC in a Brazilian public reference center, as well as the association between pCR and BC subtypes. METHODS: A retrospective cohort study used a comprehensive BC database from a Brazilian women's health reference center, including patients diagnosed between 2011 and 2020 who underwent NAC. We collected demographic, cancer-specific, and treatment-related data, analyzing OS and DFS based on pCR status using the semiparametric Kaplan-Meier method, with the date of BC diagnosis as the starting point. RESULTS: The study included 1,601 patients, with an average age of 49 years and a majority presenting stage IIIa disease (35%). Most had invasive nonspecial type (NST) BC (94%), and a significant portion (86.7%) exhibited a Ki-67 index <14. The overall pCR rate was 22.7%, with higher frequencies observed in the triple negative and luminal B subtypes. Patients who achieved pCR had significantly higher survival rates (89% alive vs. 61%, P<0.001) and better DFS (90% vs. 66%, P<0.001), except in the luminal A subtype, where pCR did not correlate with improved OS or DFS. CONCLUSIONS: These updated real-world data (RWD) from BC patients who underwent NAC in Brazil revealed a pCR rate of 22.7% in all cancer subtypes and stages. pCR was not associated with better outcomes in patients with luminal A, contrasting with other subtypes.

RESUMO

Visceral leishmaniasis (VL), caused by protozoa of the genus Leishmania, remains a significant public health concern due to its potentially lethal nature if untreated. Current chemotherapy options are limited by severe toxicity and drug resistance. Derivatives of 1,2,4-oxadiazole have emerged as promising drug candidates due to their broad biological activity. This study investigated the effects of novel 1,2,4-oxadiazole derivatives (Ox1-Ox7) on Leishmania infantum, the etiological agent of VL. In silico predictions using SwissADME suggest that these compounds have high oral absorption and good bioavailability. Among them, Ox1 showed the most promise, with higher selectivity against promastigotes and lower cytotoxicity towards L929 fibroblasts and J774.G8 macrophages. Ox1 exhibited selectivity indices of 18.7 and 61.7 against L. infantum promastigotes and amastigotes, respectively, compared to peritoneal macrophages. Ultrastructural analyses revealed severe morphological damage in both parasite forms, leading to cell death. Additionally, Ox1 decreased the mitochondrial membrane potential in promastigotes, as shown by flow cytometry. Molecular docking and dynamic simulations indicated a strong affinity of Ox1 for the L. infantum CYP51 enzyme. Overall, Ox1 is a promising and effective compound against L. infantum.

Assuntos

RESUMO

The aims of this study were to evaluate the doxorubicin concentration that induces toxic effects on in vitro culture of isolated mouse secondary follicles and to investigate whether resveratrol can inhibit or reduce this toxicity. Secondary follicles were isolated and cultured for 12 days in control medium (α-MEM+) or in α-MEM+ supplemented with doxorubicin (0.1 µg/ml) or different concentrations of resveratrol (0.5, 2, or 5 µM) associated with doxorubicin (0.1 µg/ml) (experiment 1). For experiment 2, follicles were cultured in α-MEM+ alone or supplemented with doxorubicin (0.3 µg/ml) or different concentrations of resveratrol (5 or 10 µM) associated or not with doxorubicin (0.3 µg/ml) (experiment 2). The endpoints analyzed were morphology (survival), antrum formation, follicular diameter, mitochondrial activity, glutathione (GSH) levels and DNA fragmentation. In the first experiment, doxorubicin (0.1 µg/ml) maintained survival and antrum formation similar to the control, while 5 µM resveratrol showed increased parameters, maintained mitochondrial activity and increased GSH levels compared to the control. In the second experiment, doxorubicin (0.3 µg/ml) reduced survival, antrum formation and follicular diameter compared to the control. Resveratrol at a concentration of 10 µM attenuated the damage caused by doxorubicin by improving follicular survival and did not present DNA fragmentation. In conclusion, supplementation of the in vitro culture medium with 0.3 µg/ml doxorubicin reduced the survival and impaired the development of mouse-isolated preantral follicles. Resveratrol at 10 µM reduced doxorubicin-induced follicular atresia, without DNA fragmentation in the follicles.

Assuntos

RESUMO

OBJECTIVE: Cisplatin-based chemotherapy is widely used for the treatment of oral squamous cell carcinoma (OSCC), but drug resistance and decreased sensitivity often occur during the treatment, greatly weakening its therapeutic effect. Caveolin-1 (CAV1), a protein related to ferroptosis, is involved in regulating the resistance and sensitivity of various tumor chemotherapies. This study aims to investigate whether CAV1 can regulate the sensitivity of OSCC to cisplatin through ferroptosis. METHODS: Through bioinformatics analysis, we analyzed the expression of CAV1 in OSCC and its impact on prognosis analyzed the relationship between CAV1 and tumor immune infiltration, and verified the expression of CAV1 in OSCC through immunohistochemistry experiments. We silenced the expression of CAV1 in OSCC cells through lentiviral transfection and evaluated the cell migration and invasion abilities through wound healing and Transwell assays, respectively. CCK8 assay was used to assess the sensitivity of cells to cisplatin, and ferroptosis-related biochemical marker changes were measured. Western blot was performed to detect the expression of ferroptosis-related proteins. RESULTS: The results revealed a high expression of CAV1 in OSCC, and its high expression predicted poor prognosis in OSCC. CAV1 is associated with drug metabolism pathways in OSCC, and its expression affects the infiltration levels of various immune cells in tumors. Further experiments indicated that CAV1 can inhibit ferroptosis and cisplatin sensitivity in cancer cells, promoting their migration and invasion. CONCLUSION: CAV1 promotes the progression of OSCC and can affect the sensitivity of cisplatin by regulating cellular ferroptosis.

RESUMO

Head and neck cancer accounts for 2.8% of all cancers and a large proportion of these patients have a locally advanced stage of the disease, for which chemotherapy and radiation therapy are potentially curative treatments. Dysphagia is one of the most common chemoradiotherapy-related side effects in head and neck cancer since it can lead to life-threatening complications. Reports from the current literature suggest better swallowing outcomes with intensity-modulated radiotherapy (IMRT) compared to three-dimensional conformal radiotherapy (3DCT). However, in low-/middle-income countries, multiple healthcare access barriers to 3DCT that may lead to higher rates of chemo/radiotherapy related adverse events. This narrative review provides a comprehensive appraisal of published peer-reviewed data, as well as a description of the clinical practice in an otolaryngology referral center in Colombia, a low-income country.

RESUMO

The study aimed to evaluate the effects of supplementation with Lacticaseibacillus casei CSL3 in Swiss mice immunosuppressed with cyclophosphamide on immunological, biochemical, oxidative stress, and histological parameters. The animals were distributed into four groups (control, CSL3, cyclophosphamide, and CSL3 + cyclophosphamide), where two groups were treated with L. casei CSL3 (10 log CFU mL-1) for 30 days, and two groups received chemotherapy (days 27 and 30-total dose of 250 mg kg-1). Counts of lactic acid bacteria (LAB) and bile-resistant LAB in stool samples; blood count (erythrogram, leukogram, and platelets); serum total cholesterol levels; catalase enzyme activity; and thiobarbituric acid reactive substances (TBARS) levels in liver, kidney, and brain; IL-4 expression; IL-23, TNF-α, NF-κß in the spleen; and histological changes in the liver, kidneys, and intestine were evaluated. The CSL3 + cyclophosphamide group showed a significant increase in bile-resistant LAB counts in feces (p = 0.0001), leukocyte counts, and expression of IL-23, TNF-α, and NF-κß (p < 0.05) significantly reduced total cholesterol levels (p = 0.001) and protected liver damage of supplemented animals. For oxidative stress damage, the bacterium did not influence the results. It is concluded that the bacterium is safe at a concentration of 10 log CFU mL-1 and has probiotic potential due to its positive influence on the immune response and lipid metabolism.

RESUMO

The insulin-like growth factor-2 mRNA-binding protein 1 (IGF2BP1), a member of a conserved family of single-stranded RNA-binding proteins (IGF2BP1-3), is expressed in a broad range of fetal tissues, placenta and more than sixteen cancer types but only in a limited number of normal adult tissues. IGF2BP1is required for the transport from nucleus to cytoplasm of certain mRNAs that play essential roles in embryogenesis, carcinogenesis, and multidrug resistance (MDR), by affecting their stability, translation, or localization. The purpose of this review is to gather and present information on MDR mechanisms in cancer and the significance of IGF2BP1 in this context. Within this review, we will provide an overview of IGF2BP1, including its tissue distribution, expression, molecular targets in the context of tumorigenesis and its inhibitors. Our main focus will be on elucidating the interplay between IGF2BP1 and MDR, particularly with regard to chemoresistance mediated by ABC transporters.

RESUMO

Introduction: We conducted an extensive, sex-oriented real-world data analysis to explore the impact and safety of non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors (coxibs) on cancer treatment outcomes. This is particularly relevant given the role of the COX-2/PGE2 pathway in tumor cell resistance to chemotherapy and radiotherapy. Methods: The study applied a retrospective cohort design utilizing the TriNetX research database consisting of patients receiving cancer treatment in 2008-2022. The treated cohorts included patients who were prescribed with coxibs, aspirin or ibuprofen, while individuals in the control cohort did not receive these medicines during their cancer treatment. A 1:1 propensity score matching technique was used to balance the baseline characteristics in the treated and control cohorts. Then, Cox proportional hazards regression and logistic regression were applied to assess the mortality and morbidity risks among patient cohorts in a 5-year follow-up period. Results: Use of coxibs (HR, 0.825; 95% CI 0.792-0.859 in females and HR, 0.884; 95% CI 0.848-0.921 in males) and ibuprofen (HR, 0.924; 95% CI 0.903-0.945 in females and HR, 0.940; 95% CI 0.917-0.963 in males) were associated with improved survival. Female cancer patients receiving aspirin presented increased mortality (HR, 1.078; 95% CI 1.060-1.097), while male cancer patients also had improved survival when receiving aspirin (HR, 0.966; 95% CI 0.951-0.980). Cancer subtype specific analysis suggests coxibs and ibuprofen correlated with survival, though ibuprofen and aspirin increased emergency department visits' risk. Secondary analyses, despite limited by small cohort sizes, suggest that COX inhibition post-cancer diagnosis may benefit patients with specific cancer subtypes. Discussion: Selective COX-2 inhibition significantly reduced mortality and emergency department visit rates. Further clinical trials are needed to determine the optimal conditions for indication of coxibs as anti-inflammatory adjuvants in cancer treatment.

RESUMO

Background: The coexistence of aortic stenosis (AS) and neoplastic pathology are common due to shared risk factors with atherosclerotic disease, such as diabetes, inflammatory conditions, and smoking. Severe AS in patients with cancer requires careful assessment in order to select the appropriate therapeutic choices and their timing (i.e. valve treatment first vs. cancer treatment first). Case summary: A 66-year-old woman with a history of smoking was admitted to our centre due to heart failure (HF). During her hospitalization, severe AS with severe ventricular dysfunction and cancer were documented. Because of her severe heart disease, she was unable to receive antineoplastic treatment. Therefore, she underwent percutaneous surgery to treat the aortic valve. After that, the management of cancer became possible, which included bilateral radical mastectomy and chemotherapy.We are presenting a case of cancer coexisting with aortic stenosis and reduced left ventricle ejection fraction. In this case, we performed Transcatheter Aortic Valve Replacement (TAVR) with the aim of improving the ejection fraction, followed by chemotherapy. Discussion: Cancer patients may be further disadvantaged by AS if it interferes with their treatment by increasing the risk associated with oncologic surgery and compounding the risks associated with cardiotoxicity and HF. Clinical trials and guidelines on TAVR exclude cohorts with limited life expectancy. Hence, the correct and optimal care for cancer patients with severe AS is complex. The TAVR, for cancer patients with severe AS, can more frequently be the best clinical choice by avoiding cardiopulmonary bypass, minimal invasiveness, and therefore, shorter recovery time.

RESUMO

Collecting duct carcinoma (CDC) is a rare disease associated with a high mortality rate. The present study describes the case of a recipient of a kidney transplant with metastatic allograft CDC whose treatment was successful. The patient underwent nephrectomy, and chemotherapy with gemcitabine and cisplatin, while undergoing haemodialysis treatment and remained in remission after 6 years of follow-up. There is a lack of information about the treatment and clinical management of CDC; however, the combination of gemcitabine and cisplatin remains as first-line therapy. The challenge of this case was integrating chemotherapy sessions with dialysis therapy to maintain the effectiveness, tolerability and safety of the oncological treatment. In the present case report, the success of chemotherapy with gemcitabine and cisplatin was demonstrated in a metastatic renal allograft CDC in a patient with end-stage renal disease, with few side effects and no recurrence of the disease 6 years after the end of treatment.

RESUMO

BACKGROUND: Biliary tract cancer (BTC) is a highly heterogeneous aggressive tumor, and advanced patients have poor prognosis. This work aimed to evaluate the efficacy and safety of camrelizumab combined with chemotherapy in treating advanced BTC, and to explore predictive biomarkers for distinguishing effective population. METHODS: 183 advanced BTC patients admitted from September 2018 to September 2021 were retrospectively selected. 93 patients were treated with camrelizumab combined with chemotherapy (C+C group) and 90 patients were treated with chemotherapy alone (C group). Objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), and median overall survival (mOS) were analyzed between two groups. Peripheral blood lymphocyte subsets were assessed by flow cytometry pre- and post-treatment. RESULTS: The mPFS (6.9 months) and mOS (12.1 months) in the C+C group were significantly longer than those in the C group, which were 5.2 months and 9.8 months respectively (HR 0.46, 95% CI 0.38-0.54, p=0.017; HR 0.39, 95% CI 0.32-0.47, p=0.033). The percentage of Total T, CD4+T, natural killer (NK) cells, lymphocyte, and CD4+/CD8+ cell ratios were significantly increased in effective patients after C+C treatment, but didn't increase in progressive disease (PD) patients. Higher percentage of Total T, CD4+T, and higher CD4+/CD8+ cell ratios post-treatment were associated with longer OS. CONCLUSIONS: Camrelizumab combining chemotherapy significantly prolonged the mPFS and mOS of advanced BTC patients. Immunotherapy may improve the immune status of advanced patients, and immunotherapy efficacy might be predicted based on the peripheral blood lymphocyte subsets.

RESUMO

BACKGROUND: Gastric cancer is the fifth most common neoplasm and the third leading cause of cancer-related death worldwide. Neoadjuvant chemotherapy is recommended for Stages II-III resectable tumors, but the comparative effectiveness of minimally invasive surgery (MIS) versus open gastrectomy (OG) post-neoadjuvant therapy has not been adequately investigated. METHODS: A retrospective cohort analysis was performed on patients with clinical Stage II and III gastric adenocarcinoma who underwent neoadjuvant chemotherapy followed by either MIS or OG between 2007 and 2020. Propensity score matching was utilized to compare the clinical and surgical outcomes, morbidity, and mortality, and the influence of MIS on 3-year survival rates was evaluated. RESULTS: After matching, no statistical differences in clinical aspects were noted between the two groups. MIS was associated with increased D2 lymphadenectomy, curative intent, and complete neoadjuvant therapy. Furthermore, this therapeutic approach resulted in reduced transfusion rates and shorter hospital stays. Nonetheless, no significant differences were observed in global, clinical, or surgical complications or mortality between the two groups. Weight loss emerged as a significant risk factor for complications, but MIS did not independently affect survival rates. Extended resection and higher American Society of Anesthesiology scores were independent predictors of reduced survival. CONCLUSION: MIS after neoadjuvant chemotherapy for gastric cancer appears to be a viable option, with oncological outcomes comparable to those of OG, less blood loss, and shorter hospital stays. Although MIS did not independently affect long-term survival, it offered potential benefits in terms of postoperative recovery and morbidity. Further studies are needed to validate these findings, especially across diverse populations.

RESUMO

Breast cancer (BC) is the most common cancer in women, and is characterized by its histological and molecular heterogeneity. Luminal BC is an estrogen receptor-positive subtype, with varied clinical courses. Although BC patients are eligible for hormone therapy, both early and late relapses still occur, and thus there is a demand for new cytotoxic and selective treatment strategies for these patients. In the present study, inspired by the structure of phenylsulfonylpiperazine, a series of 20 derivatives were tested in bioassays against MCF7, MDA-MB-231 and MDA-MB-453 BC cells to discover new hit compounds. After 48 h of treatment, 12 derivatives impaired cell viability and presented significant IC50 values against at least one of the tumor lineages. Overall, the luminal BC cell line MCF7 was more sensitive to treatments. Compound 3, (4-(1H-tetrazol-1-yl)phenyl)(4-((4-chlorophenyl)sulfonyl)piperazin-1-yl)methanone, was the most promising, with IC50 = 4.48 µM and selective index (SI) = 35.6 in MCF7 cells. Compound 3 also presented significant antimigratory and antiproliferative activities against luminal BC cells, possibly by affecting the expression of genes involved in the epithelial-mesenchymal transition mechanism, upregulating E-Cadherin transcripts (CDH1). Our findings suggest that phenylsulfonylpiperazine derivatives are potential candidates for the development of new therapies, especially those targeting luminal BC.

Assuntos

RESUMO

Colorectal cancer (CRC) is one of the top 10 most common cancers worldwide and caused approximately 10 million deaths in 2022. CRC mortality has increased by 10% since 2020 and 52.000 deaths will occur in 2024, highlighting the limitations of current treatments due to ineffectiveness, toxicity, or non-adherence. The widely used chemotherapeutic agent, 5-fluorouracil (5-FU), is associated with several adverse effects, including renal, cardiac, and hepatic toxicity; mucositis; and resistance. Taurine (TAU), an essential ß-amino acid with potent antioxidant, antimutagenic, and anti-inflammatory properties, has demonstrated protective effects against tissue toxicity from chemotherapeutic agents like doxorubicin and cisplatin. Taurine deficiency is linked to aging and cancers such as breast and colon cancer. This study hypothesized that TAU may mitigate the adverse effects of 5-fluorouracil (5-FU). Carcinogenesis was chemically induced in rats using 1,2-dimethylhydrazine (DMH). Following five months of cancer progression, taurine (100 mg/kg) was administered orally for 8 days, and colon tissues were analyzed. The results showed 80% of adenocarcinoma (AC) in DMH-induced control animals. Notably, the efficacy of 5-FU showed 70% AC and TAU 50% while, in the 5-FU + TAU group, no adenocarcinoma was observed. No differences were observed in the inflammatory infiltrate or the expression of genes such as K-ras, p53, and Ki-67 among the cancer-induced groups whereas APC/ß-catenin expression was increased in the 5FU + TAU-treated group. The mitotic index and dysplasia were increased in the induced 5-FU group and when associated with TAU, the levels returned to normal. These data suggest that 5-FU exhibits a synergic anticancer effect when combined with taurine.

Assuntos