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Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is initiated by binding of the viral Spike protein to host receptor angiotensin-converting enzyme 2 (ACE2), followed by fusion of viral and host membranes. Although antibodies that block this interaction are in emergency use as early coronavirus disease 2019 (COVID-19) therapies, the precise determinants of neutralization potency remain unknown. We discovered a series of antibodies that potently block ACE2 binding but exhibit divergent neutralization efficacy against the live virus. Strikingly, these neutralizing antibodies can inhibit or enhance Spike-mediated membrane fusion and formation of syncytia, which are associated with chronic tissue damage in individuals with COVID-19. As revealed by cryoelectron microscopy, multiple structures of Spike-antibody complexes have distinct binding modes that not only block ACE2 binding but also alter the Spike protein conformational cycle triggered by ACE2 binding. We show that stabilization of different Spike conformations leads to modulation of Spike-mediated membrane fusion with profound implications for COVID-19 pathology and immunity.
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Anticorpos Neutralizantes/química , Células Gigantes/metabolismo , Glicoproteína da Espícula de Coronavírus/química , Enzima de Conversão de Angiotensina 2/química , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/imunologia , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/metabolismo , Complexo Antígeno-Anticorpo/química , Complexo Antígeno-Anticorpo/metabolismo , Sítios de Ligação , Células CHO , COVID-19/patologia , COVID-19/virologia , Cricetinae , Cricetulus , Microscopia Crioeletrônica , Células Gigantes/citologia , Humanos , Fusão de Membrana , Biblioteca de Peptídeos , Ligação Proteica , Domínios Proteicos , Estrutura Quaternária de Proteína , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismoRESUMO
BACKGROUND: Metastatic colorectal cancer (mCRC) poses a clinical challenge and requires a combination of systemic therapy and conversion surgery. Although first-line chemotherapy and targeted therapy are considered the standard treatments for mCRC, the role of primary tumor resection (PTR) in asymptomatic synchronous mCRC with unresectable metastatic lesion after initial therapy remains relatively underexplored. MATERIALS: A retrospective review was conducted from January 2015 to January 2021, involving 74 patients with synchronous mCRC who received bevacizumab plus FOFIRI as first-line systemic therapy. All 74 patients had unresectable metastatic lesions confirmed through multidisciplinary team discussion. Patient characteristics, PTR data, and radiotherapy (RT) and overall survival (OS) outcomes were analyzed. The patients were categorized into a "PTR" group and a "No PTR" group and then further stratified into "4A," "4B," and "4C" subgroups based on the initial mCRC stage. Additionally, four subgroups-namely "PTR( +)/RT( +)," "PTR( +)/RT( -)," "PTR( -)/RT( +)," and "PTR( -)/RT( -)"-were formed to assess the combined effects of PTR and RT. RESULTS: The median OS for all the patients was 23.8 months (20.5-27.1 months). The "PTR" group exhibited a significantly higher median OS of 25.9 months (21.3-30.5 months) compared with 21.4 months (15.8-27.1 months) in the "No PTR" group (p = 0.048). Subgroup analyses revealed a trend of improved survival with PTR in patients with stage IVA and IVB; however, the results were not statistically significant (p = 0.116 and 0.493, respectively). A subgroup analysis of PTR and RT combinations revealed no significant difference in median OS rates. CONCLUSION: For asymptomatic mCRC with synchronous unresectable distant metastasis, PTR following first-line therapy with bevacizumab plus FOLFIRI may provide a potential survival benefit, particularly in stage IVA/IVB patients compared with stage IVC patients. Additionally, RT for primary tumor did not provide an additional OS benefit in mCRC with unresectable metastasis. A prospective randomized trial with a larger sample size is essential to further elucidate the role of PTR in this context.
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Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab , Camptotecina , Neoplasias Colorretais , Fluoruracila , Leucovorina , Metástase Neoplásica , Humanos , Bevacizumab/uso terapêutico , Bevacizumab/administração & dosagem , Neoplasias Colorretais/patologia , Neoplasias Colorretais/tratamento farmacológico , Masculino , Feminino , Leucovorina/uso terapêutico , Leucovorina/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pessoa de Meia-Idade , Fluoruracila/uso terapêutico , Fluoruracila/administração & dosagem , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Camptotecina/administração & dosagem , Idoso , Adulto , Estudos Retrospectivos , Resultado do Tratamento , Doenças AssintomáticasRESUMO
BACKGROUND: Intracorporeal anastomosis offers notable advantages over extracorporeal techniques, including reduced tissue manipulation leading to faster recovery and potentially lower risks of surgical site infections and complications. However, it also involves several challenges, such as increased operative time and the need for experienced assistants and multiple trocars. Our novel technique addresses these problems. METHODS: We present a novel approach for closing common enterotomies during intracorporeal anastomosis by using a linear stapler. This technique involves the use of a 6-cm straight needle, which facilitates closure of the common enterotomy. The technique can be performed independently by a single surgeon without the need for additional trocars or assistants. RESULTS: This technique was applied for 20 patients undergoing laparoscopic gastrointestinal surgery between June 2023 and February 2024. The median age of the enrolled patients was 65 years, with laparoscopic right hemicolectomy with intracorporeal ileocolostomy being the most common procedure (60% of cases). The median anastomosis time was 22.5 min. No occurrence of anastomotic leakage was reported, and only one patient (5%) developed temporary postoperative bowel obstruction, which was managed conservatively. CONCLUSIONS: Our technique enables efficient and safe closure of common enterotomies during intracorporeal anastomosis, minimizing reliance on additional trocars and experienced assistants. It simplifies the procedure and ensures fullthickness stapling, potentially reducing the likelihood of complications. Because of its broad applicability across various laparoscopic surgeries, this technique offers substantial benefits and is worth recommending for intracorporeal anastomosis.
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PURPOSE: To evaluate the rate of and time to complete vascularization in premature infants and to explore associated factors. METHODS: A monocentric, retrospective cohort study including 541 premature infants who underwent screening for retinopathy of prematurity (ROP) between July 2016 and June 2019. Patients underwent regular dilated fundus examinations with indirect ophthalmoscopy until complete vascularization. The worse eye of each patient was included for analyses. The proportion of infants with complete retinal vascularization at the last visit and the time to full vascularization was analyzed. RESULTS: Among all infants (average gestational age 31.29 ± 3.12 weeks), 490 (90.57%) had complete records of retinal vascularization outcomes, of whom 439 (89.59%) achieved complete vascularization. The average postmenstrual age for complete vascularization was 45.39 ± 11.04 weeks, and 95.22% achieved completion before 64 weeks of postmenstrual age. Retinopathy of prematurity developed in 118 (22.56%) infants; 33 (6.10%) received antivascular endothelial growth factor treatment. For all infants screened for ROP, lower birth weight, presence of ROP, and antivascular endothelial growth factor therapy predicted delayed complete vascularization; for infants diagnosed with ROP, only lower birth weight predicted delayed complete vascularization. Subgroup analysis showed significant differences between patients without ROP, with untreated ROP, and with treated ROP in time to complete vascularization and its rate (99.7%, 66.2%, and 16.7%, respectively). CONCLUSION: Lower birth weight predicted delayed complete vascularization. Antivascular endothelial growth factor therapy and the presence of ROP, including ROP severity, may also affect time to complete vascularization. These findings should help improve the understanding and management of persistent avascular retina in preterm infants.
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Neovascularização Retiniana , Retinopatia da Prematuridade , Lactente , Recém-Nascido , Humanos , Recém-Nascido Prematuro , Peso ao Nascer , Retinopatia da Prematuridade/diagnóstico , Estudos Retrospectivos , Fatores de Crescimento Endotelial , Neovascularização Retiniana/diagnóstico , Idade GestacionalRESUMO
Improving captive conditions of pygmy slow lorises (Nekaris and Nijman have recently suggested that the pygmy slow loris should be called the pygmy loris and is distinctive enough to warrant a new genus, Xanthonycticebu) (Nycticebus pygmeaus) poses many challenges because detailed aspects of their lives in the wild are incomplete. This hinders efforts to replicate sustainable environments for them. To improve their well-being in captivity, eight rescued female pygmy slow lorises at the Japan Monkey Center (JMC) were socially housed in two types of groups following their solitary housing: two pairs and one group of four individuals. They spent much of their time in affiliative behaviors, as well as sharing sleeping sites after placement in a social group. The purpose of my study was to examine whether social housing helped in reducing stress by comparing fecal glucocorticoids and stereotypic behaviors when housed alone and when with conspecifics. Overall, the levels of fecal glucocorticoids were significantly lower when socially housed than when kept alone. One individual exhibited stereotypic behavior when housed alone, but this behavior disappeared after social housing. These findings support recent evidence that pygmy slow lorises are social animals and will benefit from group housing in captivity. We conclude that social housing of pygmy slow lorises improves their well-being by reducing stress levels, and that their group housing in captivity can provide dividends for the conservation of this endangered nocturnal primate because lorises intended for release should find it easier to adapt to natural conditions.
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Lorisidae , Animais , Feminino , Glucocorticoides , Comportamento Estereotipado , Primatas , FezesRESUMO
BACKGROUND: Systemic therapy is the standard treatment for unresectable colorectal cancer with liver metastasis (CRCLM). Transarterial chemoembolization with drug-eluting beads (DEB-TACE) is considered an effective treatment option for CRCLM. Few studies have investigated the combination of DEB-TACE, chemotherapy, and targeted therapy for CRCLM. In the present study, we evaluated the disease control rate (DCR), adverse events, and survival among patients with CRCLM who underwent the combination of DEB-TACE and chemotherapy/targeted therapy. MATERIALS: We retrospectively reviewed 35 patients with CRCLM who were treated between January 2015 and January 2021. Standard systemic chemotherapy, targeted therapy, and 66 DEB-TACE procedures were administered. Data were collected on each DEB-TACE procedure, including chemotherapy agents, tumor burden of liver metastasis, number of DEB-TACE courses, and adverse events. Patients who received DEB-TACE after failure of first-line systemic therapy were categorized into the first-line failure group. Patients who received DEB-TACE after the failure of second-line, third-line, or fourth-line therapy were categorized into the other group. Subgroup analysis was performed to compare overall survival (OS) and progression-free survival (PFS) between the two groups. RESULTS: In total, 35 patients with CRCLM (34 patients with adenocarcinoma and 1 patient with neuroendocrine carcinoma) were enrolled. In total, 13 patients (37.1%) had extrahepatic metastases at initial diagnosis. In this study, 66 DEB-TACE procedures were performed. The DCR was 54.3%. The median OS period was 47.4 months, and the estimated 3-year OS rate was 59.5%. The median PFS period was 6.3 months, and the estimated 1-year PFS rate was 20.6%. The PFS period was longer in the first-line failure group than in the other group (7.2 vs. 6.3 months). No significant difference was observed in OS between the two groups. Four episodes (6.1%) of grade 3 intra-abdominal infection were observed. CONCLUSION: The combination of chemotherapy, targeted therapy, and DEB-TACE can lead to a favorable DCR and survival outcomes in patients with CRCLM. Early intervention with DEB-TACE (i.e., after the failure of first-line therapy) has the potential to extend the PFS period in patients with CRCLM. Severe adverse events were rare and manageable. Further prospective, randomized controlled studies are warranted to obtain more conclusive findings.
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Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/patologia , Estudos Retrospectivos , Quimioembolização Terapêutica/métodos , Resultado do Tratamento , Neoplasias Colorretais/patologiaRESUMO
Background and Objectives: Approximately 5-10% of all patients with metastatic colorectal cancer (mCRC) harbor a BRAFV600E mutation. These patients exhibit distinct metastatic patterns, poor prognosis, and heterogenous survival outcomes. The findings from the TRIBE study indicated that the administration of FOLFOXIRI plus bevacizumab as first-line treatment extended the median duration of overall survival (OS). In this study, we explored the effects of UGT1A1 polymorphism on the outcomes of irinotecan dose escalation versus FOLFOXIRI plus bevacizumab in patients with BRAFV600E-mutant mCRC. Materials and Methods: We retrospectively reviewed the medical records of 25 patients who had received a diagnosis of BRAFV600E-mutant mCRC between October 2015 and August 2022. All patients underwent UGT1A1 genotyping before receiving bevacizumab plus FOLFIRI. The primary end point was progression-free survival (PFS), and secondary endpoints were OS and adverse events (AEs). The two treatment arms were compared in terms of 6-month PFS and 12-month OS. Results: Over a median follow-up duration of 15.0 (interquartile range, 10.0-30.5) months, no significant differences were noted between the treatment arms in severe AEs (SAEs), 6-month PFS, or 12-month OS (all p < 0.05). Regarding AEs, the FOLFIRI plus bevacizumab regimen was associated with a lower incidence of anorexia than was the FOLFOXIRI plus bevacizumab regimen (p = 0.042). Conclusions: Our findings indicate that FOLFIRI plus bevacizumab with irinotecan dose escalation is an effective first-line treatment regimen for patients with BRAFV600E-mutant mCRC. This regimen leads to acceptable clinical outcomes with manageable AEs. However, the effects on survival and safety outcomes could only be speculated, and further studies are needed because of the sample size, the follow-up for the OS evaluation, and the non-uniformity in all the variables considered in the two groups.
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Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , Humanos , Bevacizumab/efeitos adversos , Irinotecano/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Estudos Retrospectivos , Dados Preliminares , Camptotecina/efeitos adversos , Fluoruracila/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
Personalized treatments based on the genetic profiles of tumors can simultaneously optimize efficacy and minimize toxicity, which is beneficial for improving patient outcomes. This study aimed to integrate gene alterations associated with predictive and prognostic outcomes in patients with metastatic colorectal cancer (mCRC) with polymerase chain reaction (PCR) and in-house next-generation sequencing (NGS) to detect KRAS, NRAS, and BRAF mutations. In the present study, 41 patients with mCRC were assessed between August 2017 and June 2019 at a single institution. The overall concordance between NGS and PCR results for detecting KRAS, NRAS, and BRAF mutations was considerably high (87.8-92.7%), with only 15 discrepant results between PCR and NGS. Our companion diagnostic test analyzes KRAS, NRAS, and BRAF as a panel of CRC molecular targets; therefore, it has the advantages of requiring fewer specimens and being more time and cost efficient than conventional testing for separate analyses, allowing for the simultaneous analysis of multiple genes.
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We report a patient who presented with congenital hypotonia, hypoventilation, and cerebellar histopathological alterations. Exome analysis revealed a homozygous mutation in the initiation codon of the NME3 gene, which encodes an NDP kinase. The initiation-codon mutation leads to deficiency in NME3 protein expression. NME3 is a mitochondrial outer-membrane protein capable of interacting with MFN1/2, and its depletion causes dysfunction in mitochondrial dynamics. Consistently, the patient's fibroblasts were characterized by a slow rate of mitochondrial dynamics, which was reversed by expression of wild-type or catalytic-dead NME3. Moreover, glucose starvation caused mitochondrial fragmentation and cell death in the patient's cells. The expression of wild-type and catalytic-dead but not oligomerization-attenuated NME3 restored mitochondrial elongation. However, only wild-type NME3 sustained ATP production and viability. Thus, the separate functions of NME3 in mitochondrial fusion and NDP kinase cooperate in metabolic adaptation for cell survival in response to glucose starvation. Given the critical role of mitochondrial dynamics and energy requirements in neuronal development, the homozygous mutation in NME3 is linked to a fatal mitochondrial neurodegenerative disorder.
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Trifosfato de Adenosina , Metabolismo Energético/genética , Homozigoto , Dinâmica Mitocondrial/genética , Nucleosídeo NM23 Difosfato Quinases , Doenças Neurodegenerativas , Trifosfato de Adenosina/genética , Trifosfato de Adenosina/metabolismo , Linhagem Celular , Sobrevivência Celular , Feminino , Humanos , Masculino , Mitocôndrias/enzimologia , Mitocôndrias/genética , Mitocôndrias/patologia , Nucleosídeo NM23 Difosfato Quinases/genética , Nucleosídeo NM23 Difosfato Quinases/metabolismo , Doenças Neurodegenerativas/enzimologia , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/patologiaRESUMO
Metastatic progression is mediated by complex interactions between deregulated extracellular matrix (ECM) and cancer cells and remains a major challenge in cancer management. To investigate the role of ECM dynamics in promoting metastasis development, we developed an artificial microenvironment (AME) platform comprised of nanodot arrays of increasing diameter. Cells cultured on the platform showed increasing signs of mesenchymal-like cell transition as AME diameter increased, suggesting accurate simulation of ECM-mediated gene regulation. Gene expression was analyzed to determine genes significant to transition, which were then used to select appropriate small molecule drugs for time course treatments. Our results suggest that the platform can identify critical target genes as well as possible drug candidates. Overall, the AME platform allows for the study of intricate ECM-induced gene expression trends across metastasis development that would otherwise be difficult to visualize in vivo and may open new avenues toward successful personalized cancer management.
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Neoplasias , Microambiente Tumoral , Matriz Extracelular , Humanos , Metástase Neoplásica , Neoplasias/tratamento farmacológico , Neoplasias/genéticaRESUMO
BACKGROUND: The undertreatment of cancer pain is a global issue although many international guidelines and various studies bloom to explore the approaches in pain management. However, there is no standard care for cancer pain in routine practices. To set up a standardized procedure for improving cancer pain management in Taiwan, the Good Pain Management (GPM) program is explored to provide treatments following the US National Cancer Care Network (NCCN) Adult Cancer Pain Guideline. METHOD: Patients diagnosed with moderate-to-severe cancer pain were eligible and randomized into the GPM or control arm and observed the first 48 h to evaluate the effects of pain management between 2 arms. Pain control, adequacy of treatments, patient satisfaction, and quality of life (QoL) of eligible patients were analyzed. Ad hoc analyses based on the pain medication category were also conducted. RESULT: Fifty-one patients were enrolled, with 26 and 25 assigned to the GPM and control arms, respectively. Significant differences among the GPM and control arms were found including a greater decrease in the mean numerical rating scale (NRS) score in the GPM arm (- 4.6 vs. - 2.8), a lower proportion of moderate-to-severe pain in the GPM arm (23.2% vs. 39.8%), and a higher pain management index (PMI) score in the GPM arm (0.64 points vs. 0.33 points) (all p < 0.05). Ad hoc analyses revealed that the patient subgroups using strong opioids showed better patient satisfaction in GPM arm when compared with the same subgroup in the control arm. CONCLUSION: In summary, our study demonstrated that the implementation of a standardized pain assessment and management approach (GPM ward program) showed significant improvements on pain relief, decreased the portion of moderate-to-severe cancer pain, and increased patient satisfaction in the 1st 48 h after admission. The implementation of the GPM approach in the cancer ward may provide sooner and better improvement of cancer pain management for patients who suffered moderate-to-severe cancer pain. TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT03155516).
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Dor do Câncer/terapia , Manejo da Dor/métodos , Qualidade de Vida/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , TaiwanRESUMO
BACKGROUND: Even with significant advances in surgical techniques and treatment, salvage chemotherapy remains the major treatment strategy for patients with unresectable or metastatic gastric cancer (GC). Practical and technical advances have simplified safe and convenient use of supplemental home parenteral nutrition (HPN). We aimed to clarify the role of HPN in patients with incurable GC undergoing salvage chemotherapy. METHODS: We enrolled 25 patients with GC with a nutritional risk index (NRI) of ⦠97.5 undergoing HPN. Their nutritional status, laboratory data, and quality of life (QoL) were analyzed using the Research and Treatment of Cancer quality of life questionnaire-C30 before and after HPN administration at 0.5, 1, 2, and 3 months. We enrolled 25 patients with an NRI of > 97.5 not undergoing HPN as the control group. RESULTS: Total protein (P = 0.008), prealbumin (P < 0.001), and total cholesterol (P = 0.023) levels improved significantly after 0.5 months of HPN administration. The study group also demonstrated a marked improvement in nitrogen balance (P = 0.004) and prealbumin levels (P < 0.012) after 1 month. Gains in body weight after 1 month and body mass index after 2 months of HPN administration remained comparable with those of the control group. Global QoL scores were maintained and comparable with those of the control group. CONCLUSIONS: Supplemental HPN therapy for malnourished patients with unresectable or metastatic GC undergoing salvage chemotherapy is feasible and revealed marked improvement in nutritional status. Early HPN intervention should be considered an important part of palliative treatment for advanced GC.
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Nutrição Parenteral no Domicílio/métodos , Qualidade de Vida/psicologia , Terapia de Salvação/métodos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Estudos Prospectivos , Neoplasias Gástricas/patologiaRESUMO
PURPOSE: To report the short-term outcomes of a modified small-incision technique for implantation of scleral-fixated intraocular lenses (IOLs) using Gore-Tex sutures. METHODS: A retrospective, interventional, consecutive case series was conducted. From June 2019 to February 2020, 10 patients underwent small-incision scleral-fixated IOL implantation using Gore-Tex sutures at a tertiary referral center. Visual and anatomical outcomes and complications were recorded with a minimum follow-up period of 3 months. Surgically induced astigmatism (SIA) and IOL-induced astigmatism were measured. RESULTS: The mean follow-up duration (range) was 396 (240-573) days. Best-corrected visual acuity improved significantly from logarithm of the minimal angle of resolution (logMAR) 0.88 ± 0.65 (Snellen equivalent: 20/153) preoperation to logMAR = 0.30 ± 0.51 (Snellen equivalent: 20/40) at final follow-up (P = .008). The estimated SIA and IOL-induced astigmatism were 0.61 diopters (D) ± 0.49D and 0.40D ± 0.36D, respectively. No intraoperative complications occurred. The postoperative complications, which included ocular hypertension (20%), cystoid macular edema (30%), and vitreous hemorrhage (20%), were transient and resolved with topical medication. CONCLUSIONS: The modified small-incision technique for implantation of scleral-fixated IOLs using Gore-Tex sutures was well tolerated in all patients, with favorable postoperative visual outcomes and minimal SIA and IOL-induced astigmatism.
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Implante de Lente Intraocular , Lentes Intraoculares , Seguimentos , Humanos , Politetrafluoretileno , Complicações Pós-Operatórias , Estudos Retrospectivos , Esclera/cirurgia , Técnicas de Sutura , SuturasRESUMO
This study investigated the roles of low-molecular-weight fucoidan (LMWF) in enhancing the anti-cancer effects of fluoropyrimidine-based chemotherapy. HCT116 and Caco-2 cells were treated with LMWF and 5-FU. Cell viability, cell cycle, apoptosis, and migration were analyzed in both cell types. Potential mechanisms underlying how LMWF enhances the anti-cancer effects of fluoropyrimidine-based chemotherapy were also explored. The cell viability of HCT116 and Caco-2 cells was significantly reduced after treatment with a LMWF--5FU combination. In HCT116 cells, LMWF enhanced the suppressive effects of 5-FU on cell viability through the (1) induction of cell cycle arrest in the S phase and (2) late apoptosis mediated by the Jun-N-terminal kinase (JNK) signaling pathway. In Caco-2 cells, LMWF enhanced the suppressive effects of 5-FU on cell viability through both the c-mesenchymal-epithelial transition (MET)/Kirsten rat sarcoma virus (KRAS)/extracellular signal-regulated kinase (ERK) and the c-MET/phosphatidyl-inositol 3-kinases (PI3K)/protein kinase B (AKT) signaling pathways. Moreover, LMWF enhanced the suppressive effects of 5-FU on tumor cell migration through the c-MET/matrix metalloproteinase (MMP)-2 signaling pathway in both HCT116 and Caco-2 cells. Our results demonstrated that LMWF is a potential complementary therapy for enhancing the efficacies of fluoropyrimidine-based chemotherapy in colorectal cancers (CRCs) with the wild-type or mutated KRAS gene through different mechanisms. However, in vivo studies and in clinical trials are required in order to validate the results of the present study.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias Colorretais , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Proteínas de Neoplasias/metabolismo , Pontos de Checagem da Fase S do Ciclo Celular/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Células CACO-2 , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Fluoruracila/farmacologia , Células HCT116 , Humanos , Polissacarídeos/farmacologiaRESUMO
Backgroundand objectives: Patients with BRAF-mutated metastatic colorectal cancer have considerably poorer responses to conventional systemic treatment. The real-world effects of triplet therapy with BRAF, mitogen-activated protein kinase kinase, and epidermal growth factor receptor inhibitors in Asia have not been well-reported. Materials and Methods: This single-center case series included patients with BRAF-mutated metastatic colorectal cancer undergoing triplet therapy after failure of prior systemic treatment from 2016 to 2020. The primary outcome was progression-free survival, and secondary outcomes were overall survival, response rate, disease control rate, and adverse events. Results: Nine eligible patients with BRAF-mutated metastatic colorectal cancer receiving triplet therapy were enrolled, with a median follow-up time of 14.5 months (range, 1-26). Most patients (88.8%) had two or more prior systemic treatments, and the triplet regimen was mainly dabrafenib, trametinib, and panitumumab. The overall response rate and disease control rate were 11.1% and 33.3%, respectively. Median progression-free survival and overall survival were 2.9 and 7.4 months, respectively, and a trend toward better overall survival was found with left-sided metastatic colorectal cancer compared with right-sided disease (9.2 vs. 6.9 months, p = 0.093). Adverse events were mostly Grade 1-2, including nausea, hypertension, gastrointestinal symptoms, and skin disorders. Conclusions: In this single-center case series, triplet therapy with BRAF, mitogen-activated protein kinase kinase, and epidermal growth factor receptor inhibitors in BRAF-mutated metastatic colorectal cancer had an acceptable safety profile and reasonable efficacy.
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Neoplasias Colorretais , Terapia de Salvação , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Receptores ErbB/antagonistas & inibidores , Humanos , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Mutação , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidoresRESUMO
BACKGROUND: Although surgical resection is the main treatment for rectal cancer, the optimal surgical protocol for elderly patients with rectal cancer remains controversial. This study evaluated the feasibility of robot-assisted surgery in elderly patients with rectal cancer. PATIENTS AND METHODS: This retrospective study enrolled 156 patients aged 28-93 years diagnosed with Stage I-III rectal cancer, who underwent robot-assisted surgery between May 2013 and December 2018 at a single institution. RESULTS: In total, 156 patients with rectal cancer, including 126 non-elderly (aged < 70 years) and 30 elderly (aged ≥70 years) patients, who underwent robot-assisted surgery were recruited. Between the patient groups, the post-operative length of hospital stay did not differ statistically significantly (P = 0.084). The incidence of overall post-operative complications was statistically significantly lower in the elderly group (P = 0.002). The disease-free and overall survival did not differ statistically significantly between the two groups (P = 0.719 and 0.390, respectively). CONCLUSIONS: Robot-assisted surgery for rectal cancer was well tolerated by elderly patients, with similar results to the non-elderly patients. Oncological outcomes and survival did not depend on patient age, suggesting that robot-assisted surgery is a feasible surgical modality for treating operable rectal cancer and leads to age-independent post-operative outcomes in elderly patients.
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BACKGROUND: The application of minimally invasive surgery in patients with colorectal cancer (CRC) and a history of previous abdominal surgery (PAS) remains controversial. This retrospective study with propensity score matching (PSM) investigated the impact of PAS on robotic-assisted rectal surgery outcomes in patients with locally advanced rectal adenocarcinoma undergoing preoperative concurrent chemoradiotherapy (CCRT). METHODS: In total, 203 patients with locally advanced rectal adenocarcinoma who underwent preoperative CCRT and robotic-assisted rectal surgery between May 2013 and December 2019 were enrolled. Patients were categorized into PAS and non-PAS groups based on the PAS history. The PSM caliper matching method with 1-to-3 matches was used to match PAS patients with non-PAS. RESULTS: Of the 203 enrolled patients, 35 were PAS patients and 168 were non-PAS patients. After PSM, 32 PAS patients and 96 non-PAS patients were included for analysis. No significant between-group differences were noted in the perioperative outcomes, including median console time (165 min (PAS) vs. 175 min (non-PAS), P = 0.4542) and median operation time (275 min (PAS) vs. 290 min (non-PAS), P = 0.5943) after PSM. Postoperative recovery and overall complication rates were also similar (all P > 0.05). Moreover, the between-group differences in pathological or short-term oncological outcomes were also nonsignificant (all P > 0.05). No 30-day postoperative deaths were observed in either group. CONCLUSION: The current results indicate that robotic-assisted surgery is safe and feasible for PAS patients with locally advanced rectal adenocarcinoma undergoing preoperative CCRT. However, future prospective randomized clinical trials are required to verify these findings.
Assuntos
Adenocarcinoma , Laparoscopia , Neoplasias Retais , Procedimentos Cirúrgicos Robóticos , Adenocarcinoma/cirurgia , Humanos , Prognóstico , Pontuação de Propensão , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Total mesorectal excision (TME) with or without neoadjuvant concurrent chemoradiotherapy (CCRT) is the treatment for rectal cancer (RC). Recently, the use of conventional laparoscopic surgery (LS) or robotic-assisted surgery (RS) has been on a steady increase cases. However, various oncological outcomes from different surgical approaches are still under investigation. METHODS: This is a retrospective observational study comprising 300 consecutive RC patients who underwent various techniques of TME (RS, n = 88; LS, n = 37; Open surgery, n = 175) at a single center of real world data to compare the pathological and oncological outcomes, with a median follow-up of 48 months. RESULTS: Upon multivariate analysis, histologic grade (P = 0.016), and stage (P < 0.001) were the independent factors of circumferential resection margin (CRM) involvement. The Kaplan-Meier survival analysis determined RS, early pathologic stage, negative CRM involvement, and pathologic complete response to be significantly associated with better overall survival (OS) and disease-free survival (DFS) (all P < 0.05). Multivariable analyses observed the surgical method (P = 0.037), histologic grade (P = 0.006), and CRM involvement (P = 0.043) were the independent factors of DFS, whereas histologic grade (P = 0.011) and pathologic stage (P = 0.022) were the independent prognostic variables of OS. CONCLUSIONS: This study determined that RS TME is feasible because it has less CRM involvement and better oncological outcomes than the alternatives have. The significant factors influencing CRM and prognosis depended on the histologic grade, tumor depth, and pre-operative CCRT. RS might be an acceptable option owing to the favorable oncological outcomes for patients with RC undergoing TME.
Assuntos
Laparoscopia/métodos , Neoplasias Retais/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Idoso , Quimiorradioterapia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Terapia Neoadjuvante , Prognóstico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Gastric ectopic pancreas presenting as a submucosal tumour accounts for approximately 11% of all endoscopic ultrasonography (EUS) examinations. Definitive diagnosis through endoscopy is difficult, even with EUS-guided fine-needle aspiration biopsy for histological examination. For symptomatic patients or those with uncertain diagnosis, complete surgical resection is the primary strategy for treatment and diagnosis. Herein, we report a case of gastric ectopic pancreas treated using robotic surgery.
RESUMO
Anorectal malignant melanoma is a very rare but aggressive cancer which carries poor prognosis. Surgical intervention is the main management but whether wide local excision or abdominoperineal resection has better survival benefit remains controversial. However, robotic-assisted restorative proctectomy with coloanal anastomosis with intersphincteric resection (ISR) has not been reported yet. Hence, we presented a case with anorectal malignant melanoma treated with robotic-assisted ISR with coloanal anastomosis. The patient has satisfied post-operative life quality, and no local recurrence was noted after 3-year follow-up.