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ABSTRACT Objective: To evaluate the effect of colostrum therapy on days to start a suckling diet in newborns diagnosed with simple gastroschisis. Methods: Randomized clinical trial with newborns diagnosed with simple gastroschisis at a federal hospital in Rio de Janeiro who were randomized to receive oropharyngeal administration of 0.2mL of colostrum or a "sham procedure" during the first 3 days of life. The analysis included clinical outcomes such as days without food, days with parenteral feeding, days until the start of enteral feeding, days to reach complete enteral feeding, sepsis and length of hospital stay. Results: The onset of oral feeding (suction) in patients with simple gastroschisis in both groups occurred at a median of 15 days. Conclusion: The present study showed that there were no significant differences in the use of colostrum therapy and the number of days to the start of enteral feeding and suction diet between groups of newborns with simple gastroschisis.
RESUMO Objetivo: Avaliar o efeito da colostroterapia em dias para iniciar a dieta por sucção em recém-nascidos com diagnóstico de gastrosquise simples. Métodos: Ensaio clínico randomizado com recém-nascidos diagnosticados com gastrosquise simples em um hospital federal no Rio de Janeiro que foram randomizados para receber administração orofaríngea de 0,2mL de colostro ou "procedimento simulado", nos primeiros 3 dias de vida. A análise incluiu desfechos clínicos, como dias sem alimentação, dias com alimentação parenteral, dias para iniciar a alimentação enteral, dias para atingir a alimentação completa, sepse e tempo de internação. Resultados: O início da alimentação por via oral (sucção) na gastrosquise simples, em ambos os grupos, ocorreu com mediana de 15 dias. Conclusão: O presente estudo mostrou que não há diferenças significativas no uso de colostroterapia em dias para início de alimentação enteral e dieta por sucção entre grupos de recém-nascidos com gastrosquise simples.
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Objective To develop a new risk scoring model based on cuproptosis-related lncRNAs (CRLs) to predict the prognosis of lung squamous cell carcinoma (LUSC). Methods Data were obtained mainly from TCGA and GTEx databases. Univariate Cox, Lasso, and multivariate Cox regression analyses were conducted to determine CRLs that affect the prognosis of LUSC and establish a risk scoring model. The ability of risk score characteristics to independently predict LUSC survival was compared with that of clinical characteristics by calculating the area under the ROC curve (AUC). Immune-related functions and immune checkpoint differences were compared between high- and low-risk groups. Results Nine CRLs were selected as independent prognostic lncRNAs for LUSC, and a risk scoring model was developed. Risk score was the influence factor for the prognosis of LUSC. The AUC values predicted by the risk score model for 1-, 3-, and 5-year survival rates of patients with LUSC were 0.710, 0.718, and 0.743, respectively. The high- and low-risk groups were partly statistically different in terms of immune-related functional assays and immune checkpoint assays (P < 0.05). Conclusion The risk scoring model developed based on nine CRLs could predict the prognosis and immune therapy response of patients with LUSC in clinical practice.
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Conversion therapy has become the core in the treatment of borderline resectable or unresectable liver cancer, which provides resectable opportunities for more advanced liver cancer patients. In accordance with the first-choice treatment regimen recommended by the guidelines, the authors reported a successful case of Atezolizumab and Bevacizumab (T+A regimen) conversion therapy. The patient with initially borderline resectable advanced liver cancer was performed liver segment resection sucessfully after conversion therapy, and non-tumor recurrence was observed at postoperative 9 months. Postoperative pathological examination showed combined hepatocellular-cholangiocarcinoma, which also indicated the important value of T+A regimen in the conversion therapy of combined hepatocellular-cholangiocarcinoma.
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Lung cancer is the most lethal malignancy around the world and non-small cell lung cancer (NSCLC) accounts for 80% of all cases. Most of the NSCLC patients has "driver gene mutations" and targeted therapy achieved a relatively good efficacy, but some patients progressed or relapsed after treatment. Previous studies demonstrated that immune checkpoint inhibitor could improve the prognosis of advanced-stage NSCLC and prolong the survival time. However, the efficacy of immune therapy varies in NSCLC patients with different immune and molecular features. The efficacy of immune therapy was controversial in NSCLC patients with driver gene mutation. The present review will summarize the immune characteristics of NSCLC patients with driver mutation and the directions of immunotherapy for patients with driver mutation. .
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Humans , Carcinoma, Non-Small-Cell Lung/therapy , Immunotherapy , Lung Neoplasms/therapy , Molecular Targeted Therapy , MutationABSTRACT
Objective: To evaluate the incidence of immune checkpoint inhibitor-based combination therapy-induced liver damage in patients with primary liver cancer. Methods: Clinical data of 65 hospitalized cases of primary liver cancer treated with programmed cell death-1 its ligand programmed death-ligand 1 (PD-1/PD-L1) antibody in the Department of Infectious Diseases of the Second Affiliated Hospital of Chongqing Medical University from January 1, 2018 to March 31, 2021 were retrospectively analyzed. The degree of liver injury before and after treatment was assessed according to CTCAE v5.0. Patients were grouped according to gender, age, presence or absence of cirrhosis, baseline Child-Pugh score, BCLC stage, and treatment regimen to compare the incidence of liver injury under different conditions. The χ (2) test or rank-sum test was used for comparison among multiple groups. Results: 46 cases (70.77%) had liver damage of any grade according to the CTCAE V5.0 criteria during the treatment and observation period. All 6 cases who received standardized anti-hepatitis B virus (HBV) treatment developed liver damage. 10 (15.38%), 15 (23.08%), 19 (29.23%), and 2 (3.08%) cases had grade 1, 2, 3, and 4 liver damage respectively. There was no statistically significant difference in the incidence of liver damage between male and female patients (68.33% and 100%, P = 0.180). There was no statistically significant difference in the incidence of liver damage among different age groups (P = 0.245). The incidence of liver damage in cirrhotic and non-cirrhotic group was 72.22%, and 63.64% (P = 0.370), respectively. The incidence of liver damage in patients with baseline Child-Pugh class A, B, and C were 71.43%, 61.11% and 100%, respectively, and the difference was not statistically significant (P = 0.878). The incidence of liver damage was not statistically significantly different under different BCLC stages (P = 1.000). The incidence of liver damage in the PD-1/PD-L1 antibody monotherapy, PD-1/PD-L1 antibody combined with targeted drug therapy, and PD-1/PD-L1 antibody combined with TACE/radiofrequency ablation treatment group were 60.00%, 67.85%, and 86.67%, respectively. There was no statistically significant difference in the incidence of liver damage between the treatment regimen (P = 0.480). Conclusion: Immune checkpoint inhibitor therapy-induced liver damage is common in patients with primary liver cancer; however, it rarely severely endangers the patient's life. Additionally, patient's gender, age, presence or absence of cirrhosis, baseline liver function, BCLC stage and the immunotherapy regimen has no effect on the incidence of immune-related liver damage.
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Female , Humans , Male , Immune Checkpoint Inhibitors , Incidence , Liver Neoplasms/epidemiology , Retrospective StudiesABSTRACT
Esophageal cancer (EC) is one of the most common cancers with high morbidity and mortality rates. EC includes two histological subtypes, namely esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). ESCC primarily occurs in East Asia, whereas EAC occurs in Western countries. The currently available treatment strategies for EC include surgery, chemotherapy, radiation therapy, molecular targeted therapy, and combinations thereof. However, the prognosis remains poor, and the overall five-year survival rate is very low. Therefore, achieving the goal of effective treatment remains challenging. In this review, we discuss the latest developments in chemotherapy and molecular targeted therapy for EC, and comprehensively analyze the application prospects and existing problems of immunotherapy. Collectively, this review aims to provide a better understanding of the currently available drugs through in-depth analysis, promote the development of new therapeutic agents, and eventually improve the treatment outcomes of patients with EC.
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Lymphocyte activation gene-3 (LAG-3, CD223) is a class of immunosuppressive receptors, mainly expressed on the cell surface of activated T and natural killer (NK) cells. As with programmed death-1 (PD-1), T cell immunoglobulin domain and mucin domain-3 (TIM-3) and other immune check-points, the expression of LAG-3 in activated T cells is upregulated to prevent the occurrence of autoimmune diseases. In the tumor microenvironment, persistent antigenic stimulation can induce T cells to overexpress LAG-3 and other suppressor molecules, causing local immune suppression in the tumor microenvironment. However, the mechanism by which LAG-3 inhibits downstream signals of T-activation or interacts with other immunosuppressive molecules is still unknown. Preliminary clinical data has shown that anti-LAG-3 and anti-PD-1 antibodies possess synergistic effect on the treatment of tumors. Moreover, LAG-3 has different intracellular domains which are completely different from those of any other immunological negative regulatory molecules, suggesting that LAG-3 might have a unique molecular mechanism and prospect of application. Currently, there are at least 7 kinds of antibody drugs targeting LAG-3 and one kind of LAG-3-Fc fusion protein in clinical research, which indicates that anti-LAG-3 targeted drugs have a broad prospect of clinical application.
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With the increase in the incidence of gastrointestinal neuroendocrine tumors(GEP-NETs),the treatment for gastrointestinal neuroendocrine tumors is gaining more attention.According to the fourth edition of the World Health Organization(WHO)digestive system tumors pathological classification in 2010,the neuroendocrine tumors can be divided into 3 levels:G1,G2,and G3,respective-ly.Among them,the G1 and G2 level are neuroendocrine tumors,G3 level is neuroendocrine carcinoma.For G1 and G2 level tumors, existing medicine treatments include somatostatin analogs,chemotherapy,targeted therapy,and interferons;while for G3 level neuro-endocrine carcinoma,platinum-based chemotherapy is generally prioritized.Recent studies have found that immune factors also con-tribute to neuroendocrine tumors.Clinical trials on immunotherapy of neuroendocrine tumors are ongoing.In this paper,the drug treatments for GEP-NETs are briefly described.
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CAR-T technology as a kind of immunotherapy, from the earliest generation of the first to the current fourth generation, its cytotoxic, anti-tumor immune effect greatly enhanced, but also challenged by safety issues.It shows a certain advantage in the therapy of Hepatocellular carcinoma. It indicates that the era of precise individual-ized liver cancer treatment, immune therapy, especially CAR-T technology combined with surgery, radiotherapy and chemotherapy, local treatment and other comprehensive treatment will play a more powerful role.
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One of the main mechanisms of tumorigenesis and development is silencing of the patient's immune response to cancer-specific antigens.The defect of cancer immune surveillance may occur at any stage of tumor progression.In the tumor micro-environment,the abnormal expression of the immune checkpoint molecules that have an activation or inhibition effect on T lymphocytes can cause immune tolerance or escape of tumor cells.Targeted immune checkpoint molecules such as PD-1(programmed cell death protein 1)and its ligand PD-L1,have been shown to be new directions for the treatment of many types of cancer.microRNAs(miR-NAs)play an important role in tumor microenvironment.Studies have shown that miRNAs are highly expressed in some tumors and play an important role in immune response,especially in early regulation.Therefore,miRNAs may be ideal candidates for the regula-tion of immune checkpoints in cancer therapy.The abnormal expression of multiple miRNAs in cancer cells provides new opportunities for cancer therapy,but the exact function of these miRNAs and their interaction with immune checkpoints are still in the exploratory phase.This review summarizes the recent findings regarding the use of miRNAs as molecular regulators of immune checkpoints and their potential applications in the treatment of cancer in clinical practice.
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Klebsiella pneumoniae is the most common cause of nosocomial respiratory tract,and the second most frequent cause of Gram-negative bacteraemia and urinary tract infections.Drug resistant isolates remain an important hospital-acquired bacterial pathogen,prolong hospital stays,and are especially problematic in high impact medical areas such as intensive care units.A variety of preventive measures were applied to reduce such incidences.The immune therapies for Klebsiella pneumoniae include active immunization and passive immunization.Many trials for constructing effective vaccines are followed,including inactivated vaccines,polysaccharide vaccine,conjugate vaccine,protein vaccine,and nano vaccine.This review was about the development of vaccines for the prevention ofKlebsiella pneumoniae.
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Klebsiella pneumoniae is the most common cause of nosocomial respiratory tract, and the second most frequent cause of Gram-negative bacteraemia and urinary tract infections. Drug resistant isolates remain an important hospital-acquired bacterial pathogen, prolong hospital stays, and are especially problematic in high impact medical areas such as intensive care units. A variety of preventive measures were applied to reduce such incidences. The immune therapies for Klebsiella pneumoniae include active immunization and passive immunization. Many trials for constructing effective vaccines are followed, including inactivated vaccines, polysaccharide vaccine, conjugate vaccine, protein vaccine, and nano vaccine. This review was about the development of vaccines for the prevention of Klebsiella pneumoniae.
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Objective To study the influence of highly efficient antiretrovirus combined with anti-immune therapy on the im-mune function and metabolism in the patients with AIDS complicating pulmonary tuberculosis (TB) .Methods 170 patients with AIDS complicating pulmonary TB from May 2013 to May 2013 were selected and divided into the observation group and control group according to the random number table method ,85 cases in each group .The control group was given highly efficient antiretro-virus and conventional anti-TB medication therapy ,while on this basis the observation group was combined with anti-immune thera-py .Then the indicators of immune function ,lipid metabolism ,toxic and side reactions were compared between two groups .Results The CD4+ and CD4/CD8+ levels after 6-month treatment in the observation group were significantly higher than those in the con-trol group(P<0 .05) ,the CD8+ level was significantly lower than that in the control group(P<0 .01);Serum total cholesterol ,tria-cylglycerol and low density lipoprotein cholesterol levels in the observation group were significantly lower than those in the control group(P<0 .05) ,the high density lipoprotein cholesterol level was significantly higher than that in the control group (P<0 .01);the occurrence rate of toxic reactions and side effects such as nausea and vomiting in the observation group was 14 .12% ,which was significantly lower than 27 .06% in the control group(χ2 =4 .353 ,P<0 .05) .Conclusion Highly efficient antiretrovirus combined with anti-immune therapy is conducive to improve the immune function in the patients with AIDS complicating pulmonary TB ,de-creases its influence on the body metabolism ,and reduces the digestive tract reactions such as nausea and vomiting .
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In recent years, immune therapy for the treatment of cancer has made remarkable progress. The monoclonal antibodies of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) have shown considerable responses and good tolerance in the treatment of non-small cell lung cancer (NSCLC). In this review, we summarized the current clinical status and future direction of PD-1/PD-L1 in NSCLC.
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@#Uveal melanoma(UM)is the most common primary intraocular malignant tumor of adult. The traditional treatment is enucleation, but it cannot completely avoid metastasis, and on the contrary, it stimulates to distant metastasis of tumor cells to some extent. According to the statistic of latest 30a, survival rates of UM patients with metastasis is still very low. Recently, many researches devoted to targeted therapy, immune therapy and radiotherapy, which have achieved gratifying results. We summarized these relative researches in this paper.
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Abstract The epithelial ovarian cancer (EOC) has been underdiagnosed because it does not have a specific clinical presentation, and the signs and symptoms are similar to the irritable bowel syndrome and pelvic inflammatory disease. EOC is less common than breast and cervical cancer, but it is more lethal. On the whole, EOC has an early dissemination to peritoneal cavity, which delays a timely diagnosis and increases the rate of advanced diagnosed disease. The diagnosis usually surprises the women and the primary care physician. Therefore, it is necessary to count on prevention and early diagnosis programs. EOC has 80% response to surgical treatment, but nearly 70% of the patients may relapse in five years. The objectives of this document are presenting a summary of the EOC epidemiology and comment about advancements in prevention, diagnosis, and treatment of this cancer. That will raise awareness about the importance of this disease.
Resumen El cáncer ovárico epitelial (COE) ha sido subdiagnosticado debido a que no tiene presentación clínica específica y a que los signos y síntomas son similares al síndrome de colon irritable y a la enfermedad inflamatoria pélvica. Es menos común que el cáncer de mama o el cervicouterino, pero es más letal. En general, tiene diseminación temprana a cavidad peritoneal, lo cual retrasa un pronóstico oportuno e incrementa la tasa de diagnóstico de enfermedad avanzada. Usualmente, el diagnóstico sorprende a la mujer y al médico de primer contacto. Entonces, es necesario contar con programas de prevención y diagnóstico temprano. El COE tiene 80% de respuesta quirúrgica, pero cerca de 70% de las pacientes puede recaer en cinco años. Los objetivos de este documento son presentar un resumen de la epidemiología del COE y comentar los avances en prevención, diagnóstico y tratamiento de este cáncer. Esto despertará la conciencia acerca de la importancia de esta enfermedad.
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Humans , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Young Adult , Ovarian Neoplasms/epidemiology , Carcinoma/epidemiology , Ovarian Neoplasms/therapy , Peritoneal Neoplasms/secondary , Carcinoma/diagnosis , Carcinoma/therapy , Ovariectomy , Combined Modality Therapy , Early Detection of Cancer , Immunotherapy , Mexico/epidemiology , Neoplasm StagingABSTRACT
A few years ago therapeutic options in advanced melanoma were very limited and the prognosis was somber. Although recent progresses are far from providing a cure for advanced melanoma, yet these have kindled new hopes and searching for a cure does not seem unreasonable. Seven new medicines have been authorized in various regions of the world in the recent past in the therapy of advanced melanoma, over half of them acting by mechanisms involving the immune system of the host. The anti-CTLA-4 (cytotoxic T lymphocyte associated protein-4) ipilimumab has been followed by anti-PD1 (programmed death1) inhibitors, more effective and safer. Very recently, the first oncolytic immunotherapy, talimogene laherparepvec (T-VEC) has been authorized for placing on the market and a variety of combinations of the new therapies are currently being evaluated or considered. Besides, a plethora of other molecules and approaches, especially monoclonal antibodies, are in the preliminary phases of clinical investigation and are likely to bring new benefits for the treatment of this potentially fatal form of cancer.
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Programmed death-1 (PD-1) and its ligand (PD-L1) inhibitors are a novel kind of immune checkpoint blockers, which are the highlights of anti-tumor immune therapy. PD-1 inhibitors, such as nivolumab and pembrolizumab have been granted by the market authorization to treat melanoma and non-small cell lung cancer. Clinical trials of their efficacy and safety on renal cell carcinoma, bladder carcinoma and Hodgkin′s lymphoma are still in process. PD-L1 inhibitors atezolizumab, durvalumab and avelumab have been approved by FDA for treatment of urothelial carcinoma. Several other drugs are in phase I clinical trials. This paper gives a brief summary of recent advances in the studies on PD-1/PD-L1 inhibitors.
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Programmed death-1(PD-1)and its ligand(PD-L1)inhibitors are a novel kind of immune checkpoint blockers, which are the highlights of anti-tumor immune therapy. PD-1 inhibitors,such as nivolumab and pembrolizumab have been granted by the market authorization to treat melanoma and non-small cell lung cancer. Clinical trials of their efficacy and safety on renal cell carci?noma,bladder carcinoma and Hodgkin′s lymphoma are still in process. PD-L1 inhibitors atezolizumab,durvalumab and avelumab have been approved by FDA for treatment of urothelial carcinoma. Several other drugs are in phaseⅠclinical trials. This paper gives a brief summary of recent advances in the studies on PD-1/PD-L1 inhibitors.
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PURPOSE: Oropharyngeal squamous cell carcinoma (OSCC) has been recognized as an immunosuppressive disease. Various mechanisms have been proposed for immune escape, including dysregulation of immune checkpoints such as the PD-1:PD-L1 pathway. We investigated the expression of programmed cell death-ligand 1 (PD-L1) in HPV-negative and HPV-positive OSCC to determine its prevalence and prognostic relevance. MATERIALS AND METHODS: Using immunohistochemistry, 133 cases of OSCC were evaluated for expression of PD-L1. Formalin-fixed paraffin-embedded tumor samples were stained with monoclonal antibody (clone 5H1) to PD-L1. PD-L1 positivity was defined as membrane staining in ≥20% of tumor cells. Correlations between PD-L1 expression and HPV status and survival parameters were analyzed. RESULTS: Of the 133 patients, 68% showed PD-L1 expression, and 67% of patients were positive for p16 expression by immunohistochemistry. No significant difference in PD-L1 expression was observed between HPV(-) and HPV(+) tumors (61% vs. 71%, p=0.274). No significant difference in age, gender, smoking history, location of tumor origin, or stage was observed according to PD-L1 status. With a median follow-up period of 44 months, older age (≥65) (p=0.017) and T3-4 stage (p<0.001) were associated with poor overall survival (OS), whereas PD-L1 expression did not affect OS in univariate and multivariate analysis. CONCLUSION: PD-L1 expression was observed in the majority of OSCC patients regardless of HPV status. Further large prospective studies are required to determine the role of PD-L1 expression as a prognostic or predictive biomarker, and clinical studies of immune checkpoint inhibitors in OCSS are warranted regardless of HPV status.