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1.
BMC Cancer ; 24(1): 765, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926636

RESUMO

BACKGROUND: It is unclear whether hepatectomy, which ranges in invasiveness from partial to major hepatectomy, is safe and feasible for older adult patients. Therefore, we compared its postoperative complications and long-term outcomes between younger and older adult patients. METHODS: Patients who underwent hepatectomies for hepatocellular carcinoma (N = 883) were evaluated. Patients were divided into two groups: aged < 75 years (N = 593) and ≥ 75 years (N = 290). Short-term outcomes and prognoses were compared between the groups in the entire cohort. The same analyses were performed for the major hepatectomy cohort. RESULTS: In the entire cohort, no significant differences were found in complications between patients aged < 75 and ≥ 75 years, and the multivariate analysis did not reveal age as a prognostic factor for postoperative complications. However, overall survival was significantly worse in older patients, although no significant differences were noted in time to recurrence or cancer-specific survival. In the multivariate analyses of time to recurrence, overall survival, and cancer-specific survival, although older age was an independent poor prognostic factor for overall survival, it was not a prognostic factor for time to recurrence and cancer-specific survival. In the major hepatectomy subgroup, short- and long-term outcomes, including time to recurrence, overall survival, and cancer-specific survival, did not differ significantly between the age groups. In the multivariate analysis, age was not a significant prognostic factor for complications, time to recurrence, overall survival, or cancer-specific survival. CONCLUSION: Hepatectomy, including minor and major hepatectomy, may be safe and oncologically feasible options for selected older adult patients with hepatocellular carcinoma.


Assuntos
Carcinoma Hepatocelular , Estudos de Viabilidade , Hepatectomia , Neoplasias Hepáticas , Humanos , Hepatectomia/métodos , Hepatectomia/efeitos adversos , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Idoso , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Prognóstico , Resultado do Tratamento , Fatores Etários , Recidiva Local de Neoplasia/cirurgia , Adulto
2.
Surg Case Rep ; 10(1): 94, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38647617

RESUMO

BACKGROUND: Spontaneous clearance of chronic hepatitis C virus (HCV) is rare in adults. A T-lymphocyte response is thought to be involved in HCV-RNA clearance. Splenectomy reportedly has a beneficial effect on T cell immune function in patients with cirrhosis. To the best of our knowledge, the present report is the first to describe spontaneous clearance of serum HCV-RNA within 1 year after splenectomy in a patient with cirrhosis. CASE PRESENTATION: A 55-year-old man with HCV cirrhosis was transferred to our institution with advanced pancytopenia, splenomegaly, and gastric varices. He had a 1-year history of ascites, edema, and general fatigue. The patient had a Child-Pugh score of 8 and serological type 1 HCV; the HCV-RNA level was 4.7 log IU/mL. Contrast-enhanced computed tomography showed gastric varices and marked splenomegaly (estimated spleen volume of 2175 mL). Esophagogastroduodenoscopy revealed enlarged gastric varices with no red color sign, and the varices were larger than those 1 year prior. He was diagnosed with decompensated HCV-related liver cirrhosis and portal hypertension. We considered direct-acting antiviral (DAA) therapy; however, DAA therapy was not approved in Japan for patients with decompensated cirrhosis at that time. Hand-assisted laparoscopic splenectomy was performed to improve the worsening portal hypertension. Further, we planned the initiation of DAA therapy after surgery, when such therapy would become available. DAA therapy was approved 1 year after splenectomy. At that time, we measured the HCV-RNA level before the initiation of DAA therapy; unexpectedly, however, serum HCV-RNA was not detectable, and the virus continued to disappear during the following 4 years. His liver function (total bilirubin, albumin, and prothrombin time) and pancytopenia improved during the 5 years postoperatively. The serum aspartate and alanine aminotransferase levels normalized between 1 and 5 years postoperatively. Esophagogastroduodenoscopy showed no change in the gastric varices during the 5 years after surgery. The patient remained asymptomatic and continued to do well. CONCLUSIONS: We have presented a case of spontaneous clearance of HCV-RNA after splenectomy in a patient with cirrhosis and portal hypertension. Splenectomy may be associated with disappearance of HCV-RNA based on previous reports. More cases should be accumulated and evaluated.

4.
J Artif Organs ; 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38051434

RESUMO

Presepsin, which is used as a biomarker for sepsis, is thought to be removed by dialysis, but the actual removal properties of dialysis are unknown. We investigated the presepsin removal properties of continuous hemodiafiltration using the high concentration of presepsin from human plasma drained by plasma exchange. Each solution in plasma exchange was connected to a continuous hemodiafiltration blood circuit and circulated at 4 conditions. The results show that presepsin was confirmed to be removed more efficiently in hemofiltration than in hemodialysis. In addition, when using a polymethylmethacrylate hemofilter for continuous hemodiafiltration, the lowest presepsin concentration is on the filtrate side, suggesting that the main removal mechanism is adsorption. Since presepsin has a molecular weight of 13,000, its removal efficiency is high by hemofiltration as per principle. In addition, since the main adsorption principle of polymethylmethacrylate hemofilter is hydrophobic bond, presepsin is considered to be adsorbed. Since presepsin is metabolized in the kidney, it is elevated in renal failure. In this paper, we confirmed that presepsin is eliminated by continuous hemodiafiltration not only in the kidney. Depending on the timing of presepsin measurement, there is a risk of missing the diagnosis of sepsis. Kidney function and continuous hemodiafiltration should be checked when measuring presepsin.

5.
Intractable Rare Dis Res ; 12(3): 198-201, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37662623

RESUMO

Hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) is an intractable neurological disease with autosomal dominant inheritance, four-limb weakness, sensory impairment, and a slowly progressive course. HMSN-P patients develop four-limb paralysis at the advanced-stage, as in amyotrophic lateral sclerosis (ALS). There is a natural 20- to 30-year course from initial painful muscle cramps and four-limb paralysis to respiratory dysfunction. A delay in the diagnosis of HMSN-P occurs due to the 20- to 30-year span from the initial symptom(s) to typical quadriplegia. Its early diagnosis is important, but the involvement of painful muscle cramps as an early symptom has not been clear. Following our earlier survey, we conducted a re-survey focusing on painful muscle cramps, assistive-device use, and hope for specific therapies in 16 Japanese patients with advanced-stage HMSN-P. Fifteen patients presented painful muscle cramps as the initial symptom, and muscle cramps in the lower abdomen including the flank were described by 10 of the patients. The presence of painful muscle cramps including those in the abdominal region may be a clue for the early diagnosis of HMSN-P. Painful abdominal cramps have not described in related diseases, e.g., ALS, spinal muscular atrophy, and Charcot-Marie-Tooth disease. Recent patient-welfare improvements and advances in assistive devices including robot-suit assistive limbs are delaying the terminal state of HMSN-P. Regarding specific therapies for HMSN-P, many patients choose both nucleic acid medicine and the application of induced pluripotent stem cells as a specific therapy for HMSN-P.

6.
Molecules ; 28(16)2023 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-37630384

RESUMO

Tolyporphins were discovered some 30 years ago as part of a global search for antineoplastic compounds from cyanobacteria. To date, the culture HT-58-2, comprised of a cyanobacterium-microbial consortium, is the sole known producer of tolyporphins. Eighteen tolyporphins are now known-each is a free base tetrapyrrole macrocycle with a dioxobacteriochlorin (14), oxochlorin (3), or porphyrin (1) chromophore. Each compound displays two, three, or four open ß-pyrrole positions and two, one, or zero appended C-glycoside (or -OH or -OAc) groups, respectively; the appended groups form part of a geminal disubstitution motif flanking the oxo moiety in the pyrroline ring. The distinct structures and repertoire of tolyporphins stand alone in the large pigments-of-life family. Efforts to understand the cyanobacterial origin, biosynthetic pathways, structural diversity, physiological roles, and potential pharmacological properties of tolyporphins have attracted a broad spectrum of researchers from diverse scientific areas. The identification of putative biosynthetic gene clusters in the HT-58-2 cyanobacterial genome and accompanying studies suggest a new biosynthetic paradigm in the tetrapyrrole arena. The present review provides a comprehensive treatment of the rich science concerning tolyporphins.


Assuntos
Glicosídeos Cardíacos , Cianobactérias , Porfirinas , Tetrapirróis , Cianobactérias/genética , Porfirinas/farmacologia
7.
World J Surg Oncol ; 21(1): 268, 2023 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-37626381

RESUMO

BACKGROUND: Frailty has been globally recognized as a predictor of adverse postoperative outcomes. Frailty assessment using the five-factor modified frailty index (5-mFI) has recently gained traction; however, long-term outcomes are unknown in colorectal cancer (CRC) surgery. This study aimed to investigate whether the 5-mFI predicted long-term survival and cause of death on the basis of frailty severity in elderly patients who underwent CRC surgery and to determine the risk factors for mortality. METHODS: A total of 299 patients underwent CRC surgery with curative intent between January 2013 and December 2017. Patients were divided into three groups by the 5-mFI score: group 1 (5-mFI: 0 or 1; n = 164): no frailty; group 2 (5-mFI: 2; n = 91): moderate frailty; and group 3 (5-mFI: ≥ 3; n = 44): severe frailty. Clinicopathological variables, namely comorbidities, 5-mFI, prognostic nutrition index, operative/postoperative data, and outcome, including cause of death, were compared between the three groups. To identify factors associated with death from CRC- and non-CRC-related causes, univariate and multivariate analyses using a Cox regression model were performed. RESULTS: The immediate postoperative morbidity of patients with Clavien-Dindo grade ≥ III complications (9.1%) in group 3 was not significantly different from that in group 1 (9.1%) or group 2 (14.3%); however, the 30-day mortality rate (4.5%) in group 3 was significantly higher. Long-term disease-free survival was similar between frailty groups, suggesting that CRC surgery provides oncological benefit to patients irrespective of frailty. The 5-year survival rates in groups 1, 2, and 3 were 83.5%, 71.2%, and 47.9%, respectively, showing a significantly lower survival rate as frailty advanced. Sixty percent of the deaths in frail patients were due to respiratory failure and cardiovascular diseases. Multivariate analysis demonstrated that advanced age, higher 5-mFI score, and longer postoperative hospital stay were risk factors for mortality unrelated to CRC. Multivariate analysis also revealed that advanced tumor stage, carcinoembryonic antigen ≥ 5 ng/ml, undifferentiated tumor, and R1 resection were risk factors for CRC-related mortality. CONCLUSIONS: The 5-mFI score can predict postoperative short- and long-term outcomes and risk factors for mortality unrelated to CRC. Additionally, long-term survival was negatively associated with the 5-mFI score.


Assuntos
Doenças Cardiovasculares , Neoplasias Colorretais , Procedimentos Cirúrgicos do Sistema Digestório , Idoso , Humanos , Intervalo Livre de Doença , Tempo de Internação , Neoplasias Colorretais/cirurgia
8.
Int Immunopharmacol ; 118: 110077, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37011499

RESUMO

Colon cancer was the second leading cause of cancer-related deaths in Japan in 2019. The effects of geniposide isolated from Gardenia jasminoides fructus (Rubiaceae) on the azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced growth of colon tumors and changes in interleukin (IL)-1 ß, monocyte chemoattractant protein (MCP)-1, IL-10, and programmed cell death-1 (PD-1) levels in the colon were investigated. The intraperitoneal administration of AOM (10 mg/kg) on days 0 and 27 induced colorectal carcinogenesis. Free access to 1% (w/v) DSS drinking water was given to mice on days 7-15, 32-33, and 35-38. Geniposide (30 and 100 mg/kg) was orally administered on days 1-16, discontinued for 11 days (days 16 to 26), and then administered again on days 27-41. Colonic levels of cytokines, chemokine, and PD-1 were measured using by enzyme-linked immunosorbent assay (ELISA). Increases in colorectal tumor numbers and areas were significantly inhibited by geniposide. In addition, geniposide (100 mg/kg) reduced colonic levels of IL-1 ß, MCP-1, PD-1 and IL-10 by 67.4, 57.2, 100%, and 100% respectively. Cyclooxygenase (COX)-2- and thymocyte selection high mobility group box proteins (TOX/TOX2)-positive cell numbers were significantly reduced by geniposide. Geniposide (30 and 100 mg/kg) decreased the phosphorylation of signal transducer and activator of transcription 3 (STAT3) expressions in immunohistochemical analysis by 64.2 and 98.2%, respectively. Thus, the inhibitory effects of geniposide on colon tumor growth may be associated with reductions in the colonic levels of IL-1 ß, MCP-1, IL-10, and PD-1 via the down-regulated expression of COX-2 and TOX/TOX2 through the inhibition of Phospho-STAT3 expression (in vivo and in vitro).


Assuntos
Colite , Neoplasias do Colo , Animais , Camundongos , Ciclo-Oxigenase 2 , Azoximetano , Interleucina-10 , Interleucina-1beta/efeitos adversos , Sulfato de Dextrana , Quimiocina CCL2 , Receptor de Morte Celular Programada 1 , Timócitos , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Colite/induzido quimicamente , Camundongos Endogâmicos C57BL
9.
Eur J Pharmacol ; 947: 175680, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-36990263

RESUMO

Colon cancer was the second leading cause of cancer-related death in 2019. We herein investigated the effects of acertannin containing Acer species on azoxymethane (AOM)/dextran sulfate sodium (DDS)-induced colon cancer growth and changes in the colonic levels of interleukin (IL)-1ß, monocyte chemoattractant protein (MCP)-1, IL-10, and programmed cell death-1 (PD-1). Colorectal carcinogenesis was induced by an intraperitoneal injection of AOM (10 mg/kg) on days 0 and 27. Mice were given 1% (w/v) DSS drinking water ad libitum on days 7-14, 32-33, and 35-38. Acertannin (30 and 100 mg/kg) was orally administered on days 1-16, discontinued for 11 days (days 16-26), and then administered again on days 27-41. The colonic levels of cytokines, a chemokine, and PD-1 were measured using the respective ELISA kits. The number and area of tumors in mice treated with acertannin (100 mg/kg) decreased by 53.9 and 63.1%, respectively. Furthermore, the colonic levels of IL-1ß, MCP-1, IL-10, and PD-1 showed reductions of 57.3, 62.9, 62.8, and 100%, respectively, while the numbers of cyclooxygenase-2 (COX-2)-, thymocyte selection-associated high mobility group box proteins (TOX)/TOX2-, PD-1-, and signal transducer and activator of transcription 3 (STAT3) phosphorylation-positive numbers decreased by 79.6, 77.9, 93.8, and 100%, respectively. In conclusion, the inhibitory effects of acertannin on AOM/DSS-induced colon tumor growth appear to be associated with reductions in the colonic levels of IL-1ß, MCP-1, IL-10, and PD-1 through the down-regulated expression of COX-2 and TOX/TOX2 in the tumor microenvironment.


Assuntos
Neoplasias do Colo , Taninos , Animais , Camundongos , Azoximetano/toxicidade , Quimiocina CCL2/metabolismo , Colo , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/prevenção & controle , Neoplasias do Colo/metabolismo , Ciclo-Oxigenase 2/metabolismo , Sulfato de Dextrana/toxicidade , Interleucina-10/metabolismo , Interleucina-1beta/metabolismo , Camundongos Endogâmicos C57BL , Receptor de Morte Celular Programada 1/metabolismo , Microambiente Tumoral , Taninos/farmacologia
10.
J Nat Prod ; 86(4): 1087-1119, 2023 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-36848595

RESUMO

Flavonoids play diverse roles in plants, comprise a non-negligible fraction of net primary photosynthetic production, and impart beneficial effects in human health from a plant-based diet. Absorption spectroscopy is an essential tool for quantitation of flavonoids isolated from complex plant extracts. The absorption spectra of flavonoids typically consist of two major bands, band I (300-380 nm) and band II (240-295 nm), where the former engenders a yellow color; in some flavonoids the absorption tails to 400-450 nm. The absorption spectra of 177 flavonoids and analogues of natural or synthetic origin have been assembled, including molar absorption coefficients (109 from the literature, 68 measured here). The spectral data are in digital form and can be viewed and accessed at http://www.photochemcad.com. The database enables comparison of the absorption spectral features of 12 distinct types of flavonoids including flavan-3-ols (e.g., catechin, epigallocatechin), flavanones (e.g., hesperidin, naringin), 3-hydroxyflavanones (e.g., taxifolin, silybin), isoflavones (e.g., daidzein, genistein), flavones (e.g., diosmin, luteolin), and flavonols (e.g., fisetin, myricetin). The structural features that give rise to shifts in wavelength and intensity are delineated. The availability of digital absorption spectra for diverse flavonoids facilitates analysis and quantitation of these valuable plant secondary metabolites. Four examples are provided of calculations─multicomponent analysis, solar ultraviolet photoprotection, sun protection factor (SPF), and Förster resonance energy transfer (FRET)─for which the spectra and accompanying molar absorption coefficients are sine qua non.


Assuntos
Flavonas , Flavonoides , Humanos , Flavonoides/química , Plantas/química , Genisteína
11.
Molecules ; 28(3)2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36770988

RESUMO

The photosynthetic tetrapyrroles share a common structural feature comprised of a ß-ketoester motif embedded in an exocyclic ring (ring E). As part of a total synthesis program aimed at preparing native structures and analogues, 3-(3-methoxy-1,3-dioxopropyl)pyrrole was sought. The pyrrole is a precursor to analogues of ring C and the external framework of ring E. Four routes were developed. Routes 1-3 entail a Pd-mediated coupling process of a 3-iodopyrrole with potassium methyl malonate, whereas route 4 relies on electrophilic substitution of TIPS-pyrrole with methyl malonyl chloride. Together, the four routes afford considerable latitude. A long-term objective is to gain the capacity to create chlorophylls and bacteriochlorophylls and analogues thereof by facile de novo means for diverse studies across the photosynthetic sciences.


Assuntos
Pirróis , Tetrapirróis , Pirróis/química , Clorofila/química , Bacterioclorofilas/química , Fotossíntese
12.
Planta Med ; 89(7): 746-753, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36796450

RESUMO

The present study investigates the effects of acertannin on colitis induced by dextran sulfate sodium (DSS) and changes in the colonic levels of the cytokines interleukin (IL)-1ß, IL-6, IL-10, IL-23, tumor necrosis factor (TNF)-α, the chemokine monocyte chemoattractant protein (MCP)-1, and vascular endothelial growth factor (VEGF).We examine the following: inflammatory colitis was induced in mice by 2% DSS drinking water given ad libitum for 7 days. Red blood cell, platelets, and leukocyte counts and hematocrit (Ht), hemoglobin (Hb), and colonic cytokine and chemokine levels were measured. The disease activity index (DAI) was lower in DSS-treated mice orally administered acertannin (30 and 100 mg/kg) than in DSS-treated mice. Acertannin (100 mg/kg) inhibited reductions in the red blood cell count and Hb and Ht levels in DSS-treated mice. Acertannin prevented DDS-induced mucosal membrane ulceration of the colon and significantly inhibited the increased colonic levels of IL-23 and TNF-α. Our findings suggest that acertannin has potential as a treatment for inflammatory bowel disease (IBD).


Assuntos
Colite , Fator de Necrose Tumoral alfa , Camundongos , Animais , Fator de Necrose Tumoral alfa/metabolismo , Sulfato de Dextrana/efeitos adversos , Interleucina-23/efeitos adversos , Interleucina-23/metabolismo , Camundongos Endogâmicos C57BL , Fator A de Crescimento do Endotélio Vascular/efeitos adversos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colo/patologia , Citocinas/metabolismo , Modelos Animais de Doenças
13.
Planta Med ; 89(6): 637-662, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36198325

RESUMO

Phyllobilins are open-chain products of the biological degradation of chlorophyll a in higher plants. Recent studies reveal that phyllobilins exert anti-oxidative and anti-inflammatory properties, as well as activities against cancer cells, that contribute to the human health benefits of numerous plants. In general, phyllobilins have been overlooked in phytochemical analyses, and - more importantly - in the analyses of medicinal plant extracts. Nevertheless, over the past three decades, > 70 phyllobilins have been identified upon examination of more than 30 plant species. Eight distinct chromophoric classes of phyllobilins are known: phyllolumibilins (PluBs), phylloleucobilins (PleBs), phylloxanthobilins (PxBs), and phylloroseobilins (PrBs)-each in type-I or type-II groups. Here, we present a database of absorption and fluorescence spectra that has been compiled of 73 phyllobilins to facilitate identification in phytochemical analyses. The spectra are provided in digital form and can be viewed and downloaded at www.photochemcad.com. The present review describes the plant origin, molecular structure, and absorption and fluorescence features of the 73 phyllobilins, along with an overview of key medicinal properties. The review should provide an enabling tool for the community for the straightforward identification of phyllobilins in plant extracts, and the foundation for deeper understanding of these ubiquitous but underexamined plant-derived micronutrients for human health.


Assuntos
Clorofila , Plantas , Humanos , Clorofila/análise , Clorofila/química , Clorofila/metabolismo , Clorofila A/metabolismo , Plantas/metabolismo , Oxirredução , Extratos Vegetais/química , Compostos Fitoquímicos/química
14.
J Phys Chem A ; 126(50): 9353-9365, 2022 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-36508586

RESUMO

A panchromatic triad and a charge-separation unit are joined in a crossbar architecture to capture solar energy. The panchromatic-absorber triad (T) is comprised of a central free-base porphyrin that is strongly coupled via direct ethyne linkages to two perylene-monoimide (PMI) groups. The charge-separation unit incorporates a free-base or zinc chlorin (C or ZnC) as a hole acceptor (or electron donor) and a perylene-diimide (PDI) as an electron acceptor, both attached to the porphyrin via diphenylethyne linkers. The free-base porphyrin is common to both light-harvesting and charge-separation motifs. The chlorin and PDI also function as ancillary light absorbers, complementing direct excitation of the panchromatic triad to produce the discrete lowest excited state of the array (T*). Attainment of full charge separation across the pentad entails two steps: (1) an initial excited-state hole/electron-transfer process to oxidize the chlorin (and reduce the panchromatic triad) or reduce the PDI (and oxidize the panchromatic triad); and (2) subsequent ground-state electron/hole migration to produce oxidized chlorin and reduced PDI. Full charge separation for pentad ZnC-T-PDI to generate ZnC+-T-PDI- occurs with a quantum yield of ∼30% and mean lifetime ∼1 µs in dimethyl sulfoxide. For C-T-PDI, initial charge separation is followed by rapid charge recombination. The molecular designs and studies reported here reveal the challenges of balancing the demands for charge separation (linker length and composition, excited-state energies, redox potentials, and medium polarity) with the constraints for panchromatic absorption (strong electronic coupling of the porphyrin and two PMI units) for integrated function in solar-energy conversion.


Assuntos
Perileno , Porfirinas , Transporte de Elétrons , Imidas
15.
Molecules ; 27(19)2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36235037

RESUMO

The syntheses of two triads are reported. Each triad is composed of two perylene-monoimides linked to a porphyrin via an ethyne unit, which bridges the perylene 9-position and a porphyrin 5- or 15-position. Each triad also contains a single tether composed of an alkynoic acid or an isophthalate unit. Each triad provides panchromatic absorption (350-700 nm) with fluorescence emission in the near-infrared region (733 or 743 nm; fluorescence quantum yield ~0.2). The syntheses rely on the preparation of trans-AB-porphyrins bearing one site for tether attachment (A), an aryl group (B), and two open meso-positions. The AB-porphyrins were prepared by the condensation of a 1,9-diformyldipyrromethane and a dipyrromethane. The installation of the two perylene-monoimide groups was achieved upon the 5,15-dibromination of the porphyrin and the subsequent copper-free Sonogashira coupling, which was accomplished before or after the attachment of the tether. The syntheses provide relatively straightforward access to a panchromatic absorber for use in bioconjugation or surface-attachment processes.


Assuntos
Perileno , Porfirinas
16.
Sci Rep ; 12(1): 8983, 2022 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-35643725

RESUMO

Osimertinib, a third-generation EGFR-TKI, has nowadays been applied to non-small cell lung cancer harboring activated EGFR mutation with or without T790M, but ultimately develop resistance to this drug. Here we report a novel mechanism of acquired resistance to osimertinib and the reversal of which could improve the clinical outcomes. In osimertinib-resistant lung cancer cell lines harboring T790M mutation that we established, expression of multiple EGFR family proteins and MET was markedly reduced, whereas expression of AXL, CDCP1 and SRC was augmented along with activation of AKT. Surprisingly, AXL or CDCP1 expression was induced by osimertinib in a time-dependent manner up to 3 months. Silencing of CDCP1 or AXL restored the sensitivity to osimertinib with reduced activation of SRC and AKT. Furthermore, silencing of both CDCP1 and AXL increased the sensitivity to osimertinib. Either silencing of SRC or dasatinib, a SRC family kinase (SFK) inhibitor, suppressed AKT phosphorylation and cell growth. Increased expression of AXL and CDCP1 was observed in refractory tumor samples from patients with lung cancer treated with osimertinib. Together, this study suggests that AXL/SFK/AKT and CDCP1/SFK/AKT signaling pathways play some roles in acquired osimertinib resistance of non-small cell lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Acrilamidas , Compostos de Anilina , Antígenos de Neoplasias/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Moléculas de Adesão Celular/genética , Resistencia a Medicamentos Antineoplásicos/genética , Receptores ErbB/metabolismo , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/genética , Quinases da Família src/genética
17.
ChemMedChem ; 17(16): e202200286, 2022 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-35704751

RESUMO

Multidrug resistant (MDR) bacteria are an increasing public health problem. One promising alternative to the development of new antibiotics is the use of antibiotic adjuvants, which would allow the continued use of FDA-approved antibiotics that have been rendered ineffective due to resistance. Herein, we report a series of dipyrrins and pyrrole derivatives designed as analogues of prodigiosin and obatoclax, several of which potentiate the activity of colistin against Klebsiella pneumoniae, with lead compounds also potentiating colistin against Acinetobacter baumannii and Pseudomonas aeruginosa.


Assuntos
Acinetobacter baumannii , Colistina , Adjuvantes Farmacêuticos/farmacologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Colistina/farmacologia , Farmacorresistência Bacteriana Múltipla , Testes de Sensibilidade Microbiana , Prodigiosina/farmacologia , Pseudomonas aeruginosa
18.
J Gastrointest Oncol ; 13(1): 137-148, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35284116

RESUMO

Background: A reduction in complications and mortality can be observed over the last few decades among elderly patients in the early postoperative period for colorectal cancer (CRC) surgery, but long-term outcomes are largely unknown. This study aimed to investigate the long-term outcomes of elderly patients 80 years and older after CRC surgery in comparison with younger age groups. The influence of clinical, oncological, and physical parameters on outcome were retrospectively analyzed. Methods: A total of 346 patients underwent CRC surgery with curative intent between January 2013 and December 2017. Patients were divided into three age groups: younger than 60 (n=47), between 60 and 79 (n=218), and 80 and older (n=81). Clinicopathological variables including comorbidity, modified frailty index, prognostic nutrition index (PNI), operative/postoperative data, and outcome including cause of death were compared among age groups. To identify factors associated with death from CRC and other causes, univariate and multivariate analyses using the Cox proportional hazards model were performed. Results: Immediate postoperative morbidity of patients with Clavien-Dindo grades of III or greater (16.0%) and the 30-day mortality rate (2.5%) of patients 80 years and older were not statistically different from those of younger age groups. Long-term disease-free survival was also similar among age groups, suggesting CRC surgery provides oncological benefit to patients irrespective of age. Multivariate analysis revealed that R1 resection, advanced tumor stage, carcinoembryonic antigen (CEA) level of >5 ng/mL, undifferentiated tumor, and longer postoperative hospital stay were risk factors for CRC death. Long-term overall survival was significantly reduced in comparison to younger age groups. Seventy percent of deaths in elderly patients during follow-up were primarily from respiratory failure and cardiovascular disease. Multivariate analysis demonstrated that advanced age, frailty, low PNI, and open procedure were risk factors for other causes of mortality. Conclusions: Elderly patients undergoing CRC surgery appeared to enjoy similar oncological benefits as younger age groups. Since both modified frailty index and PNI were correlated with mortality unrelated to CRC, preoperative assessment of these factors can be important for predicting outcome and selecting patients for prehabilitation.

19.
Rinsho Shinkeigaku ; 62(2): 152-156, 2022 Feb 19.
Artigo em Japonês | MEDLINE | ID: mdl-35095044

RESUMO

We conducted a survey of 16 Japanese patients (9 males, 7 females) aged 48-70 years in the advanced-stage Okinawa-type neurogenic muscular atrophy (i.e. hereditary motor and sensory neuropathy with proximal dominant involvement: HMSN-P) by a questionnaire asking the patients' disease name notification, acceptance, and expectations for treatment. In amyotrophic lateral sclerosis (ALS), since symptoms such as four-limb motor weakness and respiratory disorder are serious, patients are notified of the disease name at each progression stage. Individuals with HMSN-P exhibit ALS-like severe motor paralysis, but HMSN-P shows autosomal dominant inheritance, and progresses slowly (over >30 years). Many of the present patients who had one parent with the disease were able to predict what their diagnosis would be. However, several patients stated that they could not sleep for several months due to the shock of the diagnosis and their concern about how to explain to their children that the disease is hereditary. All patients in the advanced stage of HMSN-P progress to severe proximal dominant quadriplegia and ultimately need auxiliary tools such as a wheelchair. New developments toward a specific HMSN-P treatment are expected, with methods such as nucleic acid medicine.


Assuntos
Esclerose Lateral Amiotrófica , Neuropatia Hereditária Motora e Sensorial , Idoso , Esclerose Lateral Amiotrófica/genética , Feminino , Neuropatia Hereditária Motora e Sensorial/diagnóstico , Neuropatia Hereditária Motora e Sensorial/genética , Humanos , Masculino , Pessoa de Meia-Idade , Debilidade Muscular , Atrofia Muscular , Inquéritos e Questionários
20.
Clin Breast Cancer ; 22(4): e399-e406, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34862143

RESUMO

BACKGROUND: Schizophrenia is a devastating mental disease that affects approximately 1% of the world's population. Breast cancer is the second most common type of cancer in the world that causes death in women. It is often unclear whether patients with schizophrenia receive recommended cancer treatment that met the guideline. This study characterized breast cancer treatment disruptions in schizophrenia patients and sought to identify and resolve correctable predictors of those disruptions. MATERIALS AND METHODS: A retrospective cohort study was conducted on 55 primary breast cancer patients diagnosed with schizophrenia and treated for breast cancer. We evaluated the characteristics of the breast cancer patients with schizophrenia compared to those of 610 breast cancer patients without schizophrenia. RESULTS: Compared to the control group, the schizophrenia group had significantly advanced T and N factors and disease stage. Significantly fewer patients in the schizophrenia group than in the control group received chemotherapy (P < .0001) or recommended cancer treatment (P = .0004). Within the schizophrenia group, the patients in need of ADL support were significantly less likely to receive recommended cancer treatment. CONCLUSION: Patients with schizophrenia are often diagnosed with breast cancer in advanced stages. In addition, patients with schizophrenia with reduced ADL are less likely to receive chemotherapy or recommended cancer treatment. It is highly recommended that patients with schizophrenia undergo breast cancer screening so that they can be diagnosed early and treated adequately.


Assuntos
Neoplasias da Mama , Esquizofrenia , Neoplasias da Mama/tratamento farmacológico , Detecção Precoce de Câncer , Feminino , Humanos , Estudos Retrospectivos , Esquizofrenia/epidemiologia , Esquizofrenia/terapia
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