Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 7.766
Filtrar
1.
J Med Case Rep ; 15(1): 94, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33618728

RESUMO

BACKGROUND: Arthritis is rarely reported as a paraneoplastic manifestation of occult malignancy. We report herein two cases of paraneoplastic arthritis due to occult malignancy. CASE 1: The patient was a 65-year-old woman of asian descent who was a former smoker with a history of spine surgery performed for L4/L5 degenerative disc disease. She presented with a 1-month history of oligoarthritis affecting both ankle joints and early morning stiffness of about 3 hours. Laboratory tests were positive for antinuclear antibody at a titer of 1:320 (speckled) but negative for rheumatoid factor. She was treated for seronegative spondyloarthritis and started on prednisolone without much improvement. A routine chest radiograph incidentally revealed a right lung mass which was found to be adenocarcinoma of the lung. She was treated with gefitinib and her arthritis resolved. CASE 2: The patient was a 64-year-old woman of asian descent, nonsmoker, who presented with a chief complaint of asymmetrical polyarthritis involving her right wrist, second and third metacarpophalangeal joints, and first to fifth proximal interphalangeal joints. She was treated for seronegative rheumatoid arthritis (RA) and started on sulfasalazine, with poor clinical response. Six months later, she developed abdominal pain which was diagnosed as ovarian carcinoma by laparotomy. Her arthritis resolved following treatment of her malignancy with chemotherapy. CONCLUSION: In summary, paraneoplastic arthritis usually presents in an atypical manner and responds poorly to disease-modifying antirheumatic drugs. Accordingly, we recommend screening for occult malignancy in patients presenting with atypical arthritis.


Assuntos
Antineoplásicos/uso terapêutico , Artrite/etiologia , Síndromes Paraneoplásicas/diagnóstico , Síndromes Paraneoplásicas/tratamento farmacológico , Adenocarcinoma de Pulmão/diagnóstico , Adenocarcinoma de Pulmão/tratamento farmacológico , Idoso , Carcinoma/diagnóstico , Carcinoma/tratamento farmacológico , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/tratamento farmacológico
2.
Molecules ; 26(2)2021 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-33477303

RESUMO

Cannabis sativa contains more than 500 constituents, yet the anticancer properties of the vast majority of cannabis compounds remains unknown. We aimed to identify cannabis compounds and their combinations presenting cytotoxicity against bladder urothelial carcinoma (UC), the most common urinary system cancer. An XTT assay was used to determine cytotoxic activity of C. sativa extracts on T24 and HBT-9 cell lines. Extract chemical content was identified by high-performance liquid chromatography (HPLC). Fluorescence-activated cell sorting (FACS) was used to determine apoptosis and cell cycle, using stained F-actin and nuclei. Scratch and transwell assays were used to determine cell migration and invasion, respectively. Gene expression was determined by quantitative Polymerase chain reaction (PCR). The most active decarboxylated extract fraction (F7) of high-cannabidiol (CBD) C. sativa was found to contain cannabichromene (CBC) and Δ9-tetrahydrocannabinol (THC). Synergistic interaction was demonstrated between CBC + THC whereas cannabinoid receptor (CB) type 1 and type 2 inverse agonists reduced cytotoxic activity. Treatments with CBC + THC or CBD led to cell cycle arrest and cell apoptosis. CBC + THC or CBD treatments inhibited cell migration and affected F-actin integrity. Identification of active plant ingredients (API) from cannabis that induce apoptosis and affect cell migration in UC cell lines forms a basis for pre-clinical trials for UC treatment.


Assuntos
Canabinoides , Cannabis/química , Carcinoma , Movimento Celular/efeitos dos fármacos , Citoesqueleto/metabolismo , Citotoxinas , Dronabinol , Urotélio/metabolismo , Canabinoides/química , Canabinoides/farmacologia , Carcinoma/tratamento farmacológico , Carcinoma/metabolismo , Carcinoma/patologia , Citoesqueleto/patologia , Citotoxinas/química , Citotoxinas/farmacologia , Dronabinol/química , Dronabinol/farmacologia , Humanos , Urotélio/patologia
3.
Int J Mol Sci ; 22(2)2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33478005

RESUMO

The objective was to investigate the anti-cancer effects and underlying molecular mechanisms of cytostasis which were activated by an anti-microtubule drug, ABT-751, in two urinary bladder urothelial carcinoma (UBUC)-derived cell lines, BFTC905 and J82, with distinct genetic backgrounds. A series of in vitro assays demonstrated that ABT-751 induced G2/M cell cycle arrest, decreased cell number in the S phase of the cell cycle and suppressed colony formation/independent cell growth, accompanied with alterations of the protein levels of several cell cycle regulators. In addition, ABT-751 treatment significantly hurdled cell migration and invasion along with the regulation of epithelial-mesenchymal transition-related proteins. ABT-751 triggered autophagy and apoptosis, downregulated the mechanistic target of rapamycin kinase (MTOR) and upregulated several pro-apoptotic proteins that are involved in extrinsic and intrinsic apoptotic pathways. Inhibition of autophagosome and autolysosome enhanced apoptosis was also observed. Through the inhibition of the NFκB signaling pathway, ABT-751 suppressed S-phase kinase associated protein 2 (SKP2) transcription and subsequent translation by downregulation of active/phospho-AKT serine/threonine kinase 1 (AKT1), component of inhibitor of nuclear factor kappa B kinase complex (CHUK), NFKB inhibitor alpha (NFKBIA), nuclear RELA proto-oncogene, NFκB subunit (RELA) and maintained a strong interaction between NFKBIA and RELA to prevent RELA nuclear translocation for SKP2 transcription. ABT-751 downregulated stable/phospho-SKP2 including pSKP2(S64) and pSKP2(S72), which targeted cyclin-dependent kinase inhibitors for degradation through the inactivation of AKT. Our results suggested that ABT-751 may act as an anti-cancer drug by inhibiting cell migration, invasion yet inducing cell cycle arrest, autophagy and apoptosis in distinct UBUC-derived cells. Particularly, the upstream molecular mechanism of its anticancer effects was identified as ABT-751-induced cytostasis through the inhibition of SKP2 at both transcriptional and post-translational levels to stabilize cyclin dependent kinase inhibitor 1A (CDKN1A) and CDKN1B proteins.


Assuntos
Carcinoma/tratamento farmacológico , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p27/genética , Proteínas Quinases Associadas a Fase S/genética , Transcrição Genética/efeitos dos fármacos , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Carcinoma/genética , Carcinoma/patologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Fosfatidilinositol 3-Quinase/genética , Inibidores de Proteínas Quinases/farmacologia , Proteínas Quinases Associadas a Fase S/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Sulfonamidas/farmacologia , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/patologia , Urotélio/efeitos dos fármacos , Urotélio/patologia
4.
Int J Mol Sci ; 22(2)2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33430352

RESUMO

The therapeutic benefit of immune checkpoint inhibitor monotherapy is limited to a subset of patients in urothelial carcinoma (UC). Previous studies showed the immunogenicity of cisplatin and irradiation. Here, we investigated whether chemoradiotherapy (CRT), a combination of cisplatin and irradiation, could improve the efficacy of postirradiation anti-programmed cell death 1 (PD-1) treatment in UC. In our advanced UC patient cohort, patients with CRT showed a significantly better objective response rate (75%/22%) and overall survival (88%/30% at 12 months) following later pembrolizumab therapy compared to those without. Then, we created syngeneic UC mouse models by inoculating MB49 cells s.c. in C57BL/6J mice to examine the potential of CRT to enhance antitumor immunity in conjunction with postirradiation anti-PD-1 treatment. Nonirradiated tumors of the mice treated with CRT/postirradiation anti-PD-1 treatment had a significantly slower growth rate and a significantly higher expression of cytotoxic T cells compared to those of the mice treated with anti-PD-1 treatment alone. The mice treated with CRT/postirradiation anti-PD-1 treatment showed the best survival. Mechanistically, CRT provoked strong direct cytotoxicity and increased expressions of immunogenic cell death markers in MB49 cells. Therefore, the combination of cisplatin and irradiation induces immunogenic cell death and potentiates postirradiation anti-PD-1 treatment efficacy in UC.


Assuntos
Carcinoma/tratamento farmacológico , Carcinoma/radioterapia , Cisplatino/farmacologia , Morte Celular Imunogênica/efeitos dos fármacos , Animais , Antineoplásicos Imunológicos/farmacologia , Carcinoma/genética , Carcinoma/patologia , Quimiorradioterapia , Terapia Combinada , Xenoenxertos , Humanos , Camundongos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/genética , Urotélio/efeitos dos fármacos , Urotélio/patologia , Urotélio/efeitos da radiação
6.
Eur J Endocrinol ; 184(1): K1-K5, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33112279

RESUMO

Background: Pituitary carcinomas are rare but aggressive and require maximally coordinated multimodal therapies. For refractory tumors, unresponsive to temozolomide (TMZ), therapeutic options are limited. Immune checkpoint inhibitors (ICI) may be considered for treatment as illustrated in the present case report. Case: We report a patient with ACTH-secreting pituitary carcinoma, progressive after multiple lines of therapy including chemotherapy with TMZ, who demonstrated disease stabilization by a combination of ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) ICI therapy. Discussion: Management of pituitary carcinoma beyond TMZ remains ill-defined and relies on case reports. TMZ creates, due to hypermutation, more immunogenic tumors and subsequently potential candidates for ICI therapy. This case report adds support to the possible role of ICI in the treatment of pituitary carcinoma. Conclusion: ICI therapy could be a promising treatment option for pituitary carcinoma, considering the mechanisms of TMZ-induced hypermutation with increased immunogenicity, pituitary expression of CTLA-4 and PD-L1, and the frequent occurrence of hypophysitis as a side effect of ICI therapy.


Assuntos
Adenoma Hipofisário Secretor de ACT/tratamento farmacológico , Adenoma/tratamento farmacológico , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/tratamento farmacológico , Adenoma Hipofisário Secretor de ACT/imunologia , Adenoma/imunologia , Adulto , Carcinoma/imunologia , Pontos de Checagem do Ciclo Celular/imunologia , Humanos , Ipilimumab/uso terapêutico , Masculino , Nivolumabe/uso terapêutico
7.
Lancet Oncol ; 21(6): 776-785, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32631491

RESUMO

BACKGROUND: Most patients with low-grade upper tract urothelial cancer are treated by radical nephroureterectomy. We aimed to assess the safety and activity of a non-surgical treatment using instillation of UGN-101, a mitomycin-containing reverse thermal gel. METHODS: In this open-label, single-arm, phase 3 trial, participants were recruited from 24 academic sites in the USA and Israel. Patients (aged ≥18 years) with primary or recurrent biopsy-proven, low-grade upper tract urothelial cancer (measuring 5-15 mm in maximum diameter) and an Eastern Cooperative Oncology Group performance status score of less than 3 (Karnofsky Performance Status score >40) were registered to receive six instillations of once-weekly UGN-101 (mitomycin 4 mg per mL; dosed according to volume of patient's renal pelvis and calyces, maximum 60 mg per instillation) via retrograde catheter to the renal pelvis and calyces. All patients had a planned primary disease evaluation 4-6 weeks after the completion of initial therapy, in which the primary outcome of complete response was assessed, defined as negative 3-month ureteroscopic evaluation, negative cytology, and negative for-cause biopsy. Activity (complete response, expected to occur in >15% of patients) and safety were assessed by the investigator in all patients who received at least one dose of UGN-101. Data presented are from the data cutoff on May 22, 2019. This study is registered with ClinicalTrials.gov, NCT02793128. FINDINGS: Between April 6, 2017, and Nov 26, 2018, 71 (96%) of 74 enrolled patients received at least one dose of UGN-101. 42 (59%, 95% CI 47-71; p<0·0001) patients had a complete response at the primary disease evaluation visit. The median follow-up for patients with a complete response was 11·0 months (IQR 5·1-12·4). The most frequently reported all-cause adverse events were ureteric stenosis in 31 (44%) of 71 patients, urinary tract infection in 23 (32%), haematuria in 22 (31%), flank pain in 21 (30%), and nausea in 17 (24%). 19 (27%) of 71 patients had study drug-related or procedure-related serious adverse events. No deaths were regarded as related to treatment. INTERPRETATION: Primary chemoablation of low-grade upper tract urothelial cancer with intracavitary UGN-101 results in clinically significant disease eradication and might offer a kidney-sparing treatment alternative for these patients. FUNDING: UroGen Pharma.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Carcinoma/tratamento farmacológico , Portadores de Fármacos , Neoplasias Renais/tratamento farmacológico , Mitomicina/administração & dosagem , Urotélio/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibióticos Antineoplásicos/efeitos adversos , Carcinoma/patologia , Composição de Medicamentos , Feminino , Humanos , Hidrogéis , Israel , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Mitomicina/efeitos adversos , Gradação de Tumores , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Urotélio/patologia
8.
Medicine (Baltimore) ; 99(28): e21203, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664168

RESUMO

RATIONALE: Primary fallopian tube carcinoma (PFTC) is an extremely rare but invasive malignancy with a dismal prognosis. Very few data exist on the salvage treatment for patients with PFTC. Here we report a case showing an impressive response to immunotherapy combined with chemotherapy, which have never been reported before on patients with metastatic PFTC. PATIENT CONCERNS: A 42-year-old woman, who was diagnosed with PFTC in 2010, had been failed of multiple systemic therapies and antiangiogenic therapy because of the disease recurrence and progression. DIAGNOSIS: Metastatic primary fallopian tube carcinoma. INTERVENTIONS: The patient underwent surgery in May 2010 and had multi-line chemotherapies plus an anti-vascular endothelial growth factor (anti-VEGF) monoclonal antibody for about 9 years. Due to treatment failure the patient accepted the immunotherapy with the checkpoint inhibitor, pembrolizumab, combined with nab-paclitaxel from December 2018 to April 2019. OUTCOMES: The patient showed a complete response after 6 cycles treatment. Thus far, the patient is taking pembrolizumab as maintenance and remains in good health. LESSONS: Pembrolizumab combined with chemotherapy for treatment of PFTC may provide a positive antitumor effect in multiple metastatic lesions, but more clinical evidence is needed to confirm the efficacy and safety.


Assuntos
Albuminas/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/tratamento farmacológico , Neoplasias das Tubas Uterinas/tratamento farmacológico , Paclitaxel/uso terapêutico , Adulto , Feminino , Humanos
9.
Tokai J Exp Clin Med ; 45(2): 69-74, 2020 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-32602104

RESUMO

BACKGROUND: Cancer of unknown primari (CUP) are said to account for 2% of all carcinomas. Here we report a rare case of CUP confined to the retroperitoneum. CASE PRESENTATION: A 51-year-old man consulted a nearby physician for back pain. The malignant tumor could not be denied by MRI, and she was referred to our hospital. CT and MRI revealed uneven enhanced tumor structures protruding into the L2/3 disc. Part of the tumor was continuous with the left iliopsoas muscle. A CT-guided needle biopsy was performed. Histologically, the sheet-like proliferation of atypical cells was observed. Immunohistochemistry showed that atypical cells were positive for cytokeratin AE1&3, CK7, CD10, GATA3, glypican 3, Hep Par 1, carbonic anhydrase 9 (focal), and vimentin (focal) but negative for CK20, CD56, chromogranin A, synaptophysin, TTF1, HMB45, melan A, and PSA. The pathological diagnosis was poorly differentiated carcinoma. However, it was difficult to determine the primary site from the pathological findings. Positron emission tomography (PET) scan showed no distant metastases. He was diagnosed as poorly differentiated cancer localized to the lumbar spine from the retroperitoneum. Paclitaxel plus carboplatin (TC) was started. After completing 3 kr of TC, she was hospitalized urgently due to worsening lumbago. CT and MRI at admission showed an increase in the main lesion and exacerbation of bone invasion. Radiation therapy was given for curative purposes. Eventually, he died seven months after visiting our hospital and five months after starting TC therapy. CONCLUSIONS: CUP has various disease states, and it is necessary to finish the examination immediately and shift to treatment. More effective treatment including immune checkpoint inhibitor for CUP is needed in the future.


Assuntos
Carcinoma/diagnóstico por imagem , Neoplasias Primárias Desconhecidas/diagnóstico por imagem , Neoplasias Retroperitoneais/diagnóstico por imagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Carcinoma/tratamento farmacológico , Carcinoma/patologia , Evolução Fatal , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Desconhecidas/tratamento farmacológico , Paclitaxel/administração & dosagem , Tomografia por Emissão de Pósitrons , Neoplasias Retroperitoneais/tratamento farmacológico , Neoplasias Retroperitoneais/patologia , Tomografia Computadorizada por Raios X
10.
Tokai J Exp Clin Med ; 45(2): 92-96, 2020 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-32602108

RESUMO

A 69-year-old man was referred to the hematology department for the evaluation of pancytopenia. He had been treated with radiation and epirubicin for hepatocellular carcinoma, and with docetaxel and pembrolizumab for lung adenocarcinoma. Bone marrow smears exhibited markedly increased promyelocytes, and polymerase chain reaction (PCR) study demonstrated chimeric fusion genes of PML-RARA. He was diagnosed with therapy-related acute promyelocytic leukemia (t-APL) and treated with all trans-retinoic acid (ATRA). After 30 days of ATRA treatment, complete hematological response was achieved. To the best of our knowledge, this case represents the first description of successfully treated t-APL diagnosed after treatment with pembrolizumab.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma/tratamento farmacológico , Docetaxel/efeitos adversos , Epirubicina/efeitos adversos , Leucemia Promielocítica Aguda/induzido quimicamente , Leucemia Promielocítica Aguda/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Primárias Múltiplas , Tretinoína/uso terapêutico , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Docetaxel/uso terapêutico , Epirubicina/uso terapêutico , Humanos , Masculino , Resultado do Tratamento
11.
Ned Tijdschr Geneeskd ; 1642020 06 25.
Artigo em Holandês | MEDLINE | ID: mdl-32608922

RESUMO

Preoperative chemotherapy followed by surgery was applied in three patients, aged 68 years (male), 48 years (female), and 80 years (male) with locally advanced cancer of the colon with bladder invasion. Achieving a resection with free margins (R0) is essential in colon-cancer surgery, but the role of preoperative chemotherapy in colon cancer remains unknown. When a tumour is presumed to be unresectable, guidelines recommend discussing the case and possibly referring the patient to an oncological expertise centre, where each patient will be individually assessed for the most suitable preoperative treatment and surgery during a multidisciplinary tumour board meeting. All three patients showed that preoperative chemotherapy led to down-staging and reduction of the tumour size, although removal of the bladder was still necessary in one patient. All patients underwent a complete resection, which resulted in long-term disease-free and overall survival.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma/tratamento farmacológico , Neoplasias do Colo/tratamento farmacológico , Terapia Neoadjuvante/métodos , Bexiga Urinária/patologia , Idoso , Carcinoma/patologia , Carcinoma/cirurgia , Quimioterapia Adjuvante , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Período Pré-Operatório , Resultado do Tratamento
12.
Medicine (Baltimore) ; 99(25): e19908, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32569154

RESUMO

BACKGROUND: Targeted drugs including bevacizumab, cetuximab, and panitumumab have been widely used during the management of patients diagnosed with colorectal carcinoma, especially as palliative treatment. The present meta-analysis was performed to evaluate the fatal adverse events (FAEs) of targeted drugs including bevacizumab, cetuximab, and panitumumab in patients with colorectal cancer. PATIENTS AND METHODS: Studies of prospective, randomized, and controlled feature from EMBASE, Medline, and Cochrane Library, which reported FAEs potentially associated with bevacizumab, cetuximab, and panitumumab were adopted. Clinical characteristics and FAEs were collected from the enrolled literatures, with the quality of which been evaluated. Pooled analysis of FAEs, caused by each agent as first line, second/further line, and adjuvant treatment were performed with relative risks (RRs) and their corresponding 95% confidence intervals (CIs) in software RevMan 5.3. RESULTS: Thirty-one studies including 25,939 patients were brought into the final analysis. The RR and its 95% CI of the FAEs among all the agents including bevacizumab, cetuximab, and panitumumab was 1.07 (95% CI, 0.89-1.29; P = .50). The RRs and their 95% CIs of the FAEs as first line, second or further line, and adjuvant treatment related to bevacizumab were 0.91 (95% CI, 0.62-1.32; P = .61), 1.14 (95% CI, 0.57-2.28; P = .71), and 1.10 (95% CI, 0.67-1.79; P = .72). The RRs and their 95% CIs of the FAEs as first line, second or further line, and adjuvant treatment related to cetuximab were 1.02 (95% CI, 0.60-1.76; P = .93), 2.51 (95% CI, 0.49-12.88; P = .27), and 2.40 (95% CI, 1.00-5.77; P = .05). The RRs and their 95% CIs of the FAEs as first line, second or further line treatment related to panitumumab were 1.40 (95% CI, 0.89-2.18; P = .14) and 0.68 (95% CI, 0.43-1.09; P = .11), respectively. CONCLUSIONS: The present meta-analysis did not show any significantly increased RR of FAEs belonging to bevacizumab, cetuximab, or panitumumab, whether as first line, second/further line, or adjuvant treatment among patients with colorectal carcinoma comparing to placebo or blank treatment.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Carcinoma/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Bevacizumab/efeitos adversos , Cetuximab/efeitos adversos , Humanos , Panitumumabe/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
13.
In Vivo ; 34(3 Suppl): 1667-1673, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32503827

RESUMO

BACKGROUND: COVID-19 pandemic required a marked re-allocation of healthcare resources, including at Breast Units. A patient-tailored program was developed to assess its efficacy regarding prevention of COVID-19 infection among patients with breast cancer undergoing surgery and healthcare workers (HCWs). PATIENTS AND METHODS: From March 9th to April 9th 2020, 91 patients were selected for elective surgery by means of: i) Pre-hospital screening aimed at avoiding hospitalization of symptomatic or suspicious COVID-19 patients, and ii) prioritisation of surgical procedure according to specific disease features. RESULTS: Eighty-five patients (93.4%) were fit for surgery, while five patients (5.5%) were temporarily excluded through 'telephone triage'; another two patients were excluded at in-hospital triage. A total of 71 out of 85 patients (83.5%) were diagnosed with invasive cancer, most of whom were undergoing breast-conserving surgery (61 out of 85 patients, 71.8%). The mean in-hospital stay was 2.2 days (SD=0.7 days). After hospital discharge, no patient needed re-admission due to post-operative complications; moreover, no COVID-19 infection among patients or HCWs was detected. CONCLUSION: Safe breast cancer surgery was accomplished for both patients and HCWs by means of a careful preoperative selection of patients and in-hospital preventative measures. This screening program can be transferred to high-volume Breast Units and it may be useful in implementing European Community recommendations for prevention of COVID-19 infection.


Assuntos
Neoplasias da Mama/cirurgia , Carcinoma/cirurgia , Infecções por Coronavirus/prevenção & controle , Procedimentos Cirúrgicos Eletivos/estatística & dados numéricos , Controle de Infecções/métodos , Mastectomia/estatística & dados numéricos , Pandemias/prevenção & controle , Seleção de Pacientes , Pneumonia Viral/prevenção & controle , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/enfermagem , Carcinoma/tratamento farmacológico , Carcinoma/epidemiologia , Carcinoma/enfermagem , Técnicas de Laboratório Clínico , Terapia Combinada , Infecções por Coronavirus/diagnóstico , Feminino , Unidades Hospitalares/organização & administração , Humanos , Itália/epidemiologia , Tempo de Internação/estatística & dados numéricos , Metástase Linfática/diagnóstico por imagem , Linfocintigrafia , Mastectomia Segmentar/estatística & dados numéricos , Terapia Neoadjuvante , Alta do Paciente , Equipamentos de Proteção , Biópsia de Linfonodo Sentinela , Avaliação de Sintomas , Telemedicina , Triagem
14.
Gulf J Oncolog ; 1(33): 27-30, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32476647

RESUMO

OBJECTIVE: We evaluate the seeding step of peritoneal carcinomatosis cancer as a surrogate for the role of the omentum in colorectal tumors. METHODS: The study included 5 groups of adult male Sprague Dawley rats: immunocompetent rats (group 1), immunosuppressed rats without omentectomy (group 2), immunosuppressed rats with omentectomy (group 3), immunosuppressed rats with omentectomy receiving NSAID (group 4), and immunosuppressed rats without omentectomy receiving NSAID (group 5). Except for group 1, the rats were immunosuppressed using cyclosporine orally at a dose of 25 mg/kg/day that was started 48 hours before tumor cell infiltration in the peritoneum. All the rats received an intraperitoneal suspension of 10 million Caco-2 cancer cells. Rats in groups 1, 2, and 3 were followed up without further interventions and rats in groups 4 and 5 received naproxen 180mg/kg until rat sacrifice. Cyclosporine and naproxen were continued in the corresponding groups until the killing after 21 days of tumor cell infiltration. RESULTS: Fourteen rats survived the experiment during the observation period and remained in good clinical condition except for one rat (from group 4) that deceased at week 2. At day 21 before sacrifice, mean weight variations showed a +4% in group 0, -9% in group 1, -18% in group 2, -31% in group 3 and -36% in group 4. Light microscopy did not identify any tumor cells in the abdominal cavity or thorax solid organs but showed a granulomatous reaction that involved the majority of the organs. CONCLUSION: The conclusions of this study are limited by the small number of rats as it is a pilot study to design an animal model with peritoneal carcinomatosis. Further steps in this study will include more aggressive cancer cell lines such as HT29 and more aggressive immunosuppression in a larger number of rats.


Assuntos
Carcinoma/tratamento farmacológico , Ciclosporina/uso terapêutico , Neoplasias Peritoneais/tratamento farmacológico , Animais , Ciclosporina/farmacologia , Modelos Animais de Doenças , Humanos , Masculino , Ratos , Ratos Sprague-Dawley
15.
Lancet Oncol ; 21(5): 710-722, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32359490

RESUMO

BACKGROUND: In ARIEL3, rucaparib maintenance treatment significantly improved progression-free survival versus placebo. Here, we report prespecified, investigator-assessed, exploratory post-progression endpoints and updated safety data. METHODS: In this ongoing (enrolment complete) randomised, placebo-controlled, phase 3 trial, patients aged 18 years or older who had platinum-sensitive, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube carcinoma and an Eastern Cooperative Oncology Group performance status of 0 or 1 who had received at least two previous platinum-based chemotherapy regimens and responded to their last platinum-based regimen were randomly assigned (2:1) to oral rucaparib (600 mg twice daily) or placebo in 28-day cycles using a computer-generated sequence (block size of six with stratification based on homologous recombination repair gene mutation status, progression-free interval following penultimate platinum-based regimen, and best response to most recent platinum-based regimen). Patients, investigators, site staff, assessors, and the funder were masked to assignments. The primary endpoint of investigator-assessed progression-free survival has been previously reported. Prespecified, exploratory outcomes of chemotherapy-free interval (CFI), time to start of first subsequent therapy (TFST), time to disease progression on subsequent therapy or death (PFS2), and time to start of second subsequent therapy (TSST) and updated safety were analysed (visit cutoff Dec 31, 2017). Efficacy analyses were done in all patients randomised to three nested cohorts: patients with BRCA mutations, patients with homologous recombination deficiencies, and the intention-to-treat population. Safety analyses included all patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, NCT01968213. FINDINGS: Between April 7, 2014, and July 19, 2016, 564 patients were enrolled and randomly assigned to rucaparib (n=375) or placebo (n=189). Median follow-up was 28·1 months (IQR 22·0-33·6). In the intention-to-treat population, median CFI was 14·3 months (95% CI 13·0-17·4) in the rucaparib group versus 8·8 months (8·0-10·3) in the placebo group (hazard ratio [HR] 0·43 [95% CI 0·35-0·53]; p<0·0001), median TFST was 12·4 months (11·1-15·2) versus 7·2 months (6·4-8·6; HR 0·43 [0·35-0·52]; p<0·0001), median PFS2 was 21·0 months (18·9-23·6) versus 16·5 months (15·2-18·4; HR 0·66 [0·53-0·82]; p=0·0002), and median TSST was 22·4 months (19·1-24·5) versus 17·3 months (14·9-19·4; HR 0·68 [0·54-0·85]; p=0·0007). CFI, TFST, PFS2, and TSST were also significantly longer with rucaparib than placebo in the BRCA-mutant and homologous recombination-deficient cohorts. The most frequent treatment-emergent adverse event of grade 3 or higher was anaemia or decreased haemoglobin (80 [22%] patients in the rucaparib group vs one [1%] patient in the placebo group). Serious treatment-emergent adverse events were reported in 83 (22%) patients in the rucaparib group and 20 (11%) patients in the placebo group. Two treatment-related deaths have been previously reported in this trial; there were no new treatment-related deaths. INTERPRETATION: In these exploratory analyses over a median follow-up of more than 2 years, rucaparib maintenance treatment led to a clinically meaningful delay in starting subsequent therapy and provided lasting clinical benefits versus placebo in all three analysis cohorts. Updated safety data were consistent with previous reports. FUNDING: Clovis Oncology.


Assuntos
Carcinoma/tratamento farmacológico , Indóis/administração & dosagem , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma/patologia , Progressão da Doença , Método Duplo-Cego , Feminino , Humanos , Indóis/efeitos adversos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/patologia , Platina/administração & dosagem , Platina/efeitos adversos , Inibidores de Poli(ADP-Ribose) Polimerases/administração & dosagem , Inibidores de Poli(ADP-Ribose) Polimerases/efeitos adversos , Intervalo Livre de Progressão , Resultado do Tratamento
16.
Mol Cancer Res ; 18(9): 1379-1391, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32471883

RESUMO

Ovarian cancer is an aggressive disease that affects about 300,000 patients worldwide, with a yearly death count of about 185,000. Following surgery, treatment involves adjuvant or neoadjuvant administration of taxane with platinum compounds cisplatin or carboplatin, which alkylate DNA through the same chemical intermediates. However, although platinum-based therapy can cure patients in a number of cases, a majority of them discontinues treatment owing to side effects and to the emergence of resistance. In this study, we focused on resistance to cisplatin and investigated whether metabolic changes could be involved. As models, we used matched pairs of cisplatin-sensitive (SKOV-3 and COV-362) and cisplatin-resistant (SKOV-3-R and COV-362-R) human ovarian carcinoma cells that were selected in vitro following exposure to increasing doses of the chemotherapy. Metabolic comparison revealed that resistant cells undergo a shift toward a more oxidative metabolism. The shift goes along with a reorganization of the mitochondrial network, with a generally increased mitochondrial compartment. More functional mitochondria in cisplatin-resistant compared with cisplatin-sensitive cells were associated to enzymatic changes affecting either the electron transport chain (SKOV-3/SKOV-3-R model) or mitochondrial coupling (COV-362/COV-362-R model). Our findings further indicate that the preservation of functional mitochondria in these cells could be due to an increased mitochondrial turnover rate, suggesting mitophagy inhibition as a potential strategy to tackle cisplatin-resistant human ovarian cancer progression. IMPLICATIONS: Besides classical mechanisms related to drug efflux and target modification, we report that preserving functional mitochondria is a strategy used by human ovarian cancer cells to resist to cisplatin chemotherapy.


Assuntos
Antineoplásicos/farmacologia , Carcinoma/tratamento farmacológico , Cisplatino/farmacologia , Metabolismo Energético , Neoplasias Ovarianas/tratamento farmacológico , Transdução de Sinais , Animais , Autofagia , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Carcinoma/virologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Camundongos Nus , Mitocôndrias/metabolismo , Mitofagia , Neoplasias Ovarianas/virologia , Oxirredução , Taxoides/administração & dosagem
17.
PLoS One ; 15(4): e0231633, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32353864

RESUMO

Arginine deprivation cancer therapy targets certain types of malignancies with positive result in many studies and clinical trials. NEI-01 was designed as a novel arginine-depleting enzyme comprising an albumin binding domain capable of binding to human serum albumin to lengthen its half-life. In the present work, NEI-01 is shown to bind to serum albumin from various species, including mice, rat and human. Single intraperitoneal administration of NEI-01 to mice reduced plasma arginine to undetectable level for at least 9 days. Treatment of NEI-01 specifically inhibited cell viability of MIA PaCa-2 and PANC-1 cancer cell lines, which were ASS1 negative. Using a human pancreatic mouse xenograft model, NEI-01 treatment significantly reduced tumor volume and weight. Our data provides proof of principle for a cancer treatment strategy using NEI-01.


Assuntos
Antineoplásicos/uso terapêutico , Arginina/metabolismo , Carcinoma/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Desiminases de Arginina em Proteínas/uso terapêutico , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/metabolismo , Arginina/sangue , Arginina/deficiência , Argininossuccinato Sintase/metabolismo , Linhagem Celular Tumoral , Feminino , Humanos , Injeções Intraperitoneais , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Ligação Proteica , Desiminases de Arginina em Proteínas/administração & dosagem , Desiminases de Arginina em Proteínas/metabolismo , Ratos , Albumina Sérica/metabolismo
18.
Med Oncol ; 37(5): 48, 2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-32277283

RESUMO

Therapy-related acute leukemias (t-ALs) represent approximately 10-20% of all acute leukemias, are frequently resistant to chemotherapy, and are associated with guarded outcomes. The national comprehensive cancer network data suggest that t-AL cases are diagnosed at increasing rates in breast cancer patients treated with chemotherapeutic agents targeting topoisomerase II. Two cases of BRCA1-mutated ovarian and breast carcinoma who developed therapy-related APL and ALL, respectively, following topoisomerase II-directed therapy were characterized. Genomic characterization of therapy-related acute promyelocytic leukemia (t-APL) revealed a unique RARA intron 2 breakpoint (Chr17: 40347487) at 3'-end of RARA corroborating breakpoint clustering in t-APL following topoisomerase II inhibition. Both cases of this series harbored germline BRCA1 mutations. The germline BRCA1 mutation in patient with t-APL was detected in exon 8 (HGVS nucleotide: c.512dupT). This mutation in t-APL is extremely rare. Interestingly, t-ALL patient in this series had a BRCA1 mutation (HGVS nucleotide: c.68_69delAG; BIC designation: 187delAG) identical to a previously reported case after the treatment of same primary disease. It is unlikely that two breast cancer patients with identical BRCA1 mutation receiving topoisomerase II-targeted agents for the primary disease developed t-AL by chance. This report highlights the development of t-AL in BRAC1-mutated hereditary breast and ovarian cancer patients and warrants further studies on functional consequences of topoisomerase inhibition in this setting.


Assuntos
Proteína BRCA1/genética , Carcinoma/tratamento farmacológico , Síndrome Hereditária de Câncer de Mama e Ovário/tratamento farmacológico , Leucemia Mieloide Aguda/induzido quimicamente , Inibidores da Topoisomerase II/efeitos adversos , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/genética , Carcinoma/patologia , Feminino , Mutação em Linhagem Germinativa , Síndrome Hereditária de Câncer de Mama e Ovário/genética , Síndrome Hereditária de Câncer de Mama e Ovário/patologia , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Pessoa de Meia-Idade , Proteínas de Fusão Oncogênica/genética , Inibidores da Topoisomerase II/uso terapêutico , Translocação Genética , Resultado do Tratamento
19.
Ann Thorac Surg ; 110(2): 406-413, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32268141

RESUMO

BACKGROUND: Pulmonary sarcomatoid carcinoma (PSC) is a rare type of lung cancer. This study aimed to explore the appropriate treatment for PSC. METHODS: Two cohorts were used: patients from the Surveillance, Epidemiology, and End Results (SEER) database (1988 to 2014) and Shanghai resident patients at Shanghai Pulmonary Hospital (2009 to 2019) in China. Cox regression analysis was applied to identify prognostic factors for progression-free survival and overall survival (OS). Interaction assessments were performed using likelihood ratio tests to examine relationships between adjuvant chemotherapy and other baseline characteristics. RESULTS: In the SEER cohort, 1640 patients with PSC were identified, with a median survival and a 5-year OS rate of 7 months (95% confidence interval (CI), 6 to 8 months) and 19.5%, respectively. Multivariable Cox analysis of surgically treated patients revealed that adjuvant chemotherapy was significantly associated with better survival (hazard ratio, 0.78; 95% CI, 0.62 to 0.98), and the benefit was more pronounced in T3 to T4 stage (P = .04) and N-positive patients (P < .01). In the Shanghai Pulmonary Hospital cohort (n = 175), the median progression-free survival and OS were 8 months (95% CI, 7 to 12 months) and 12 months (95% CI, 10 to 18 months), respectively, with a 5-year OS rate of 25.1%. Similarly, the survival benefit of adjuvant chemotherapy was confirmed in patients with surgical resection (hazard ratio, 0.50; 95% CI, 0.31 to 0.81), but this benefit was restricted to patients who were younger (age <63 years; P = .02) and had a higher body mass index (>25 kg/m2; P < .01) by interaction assessments. The disease control rate after chemotherapy was 58.62%, and the disease control rate after targeted therapy was 57.14%. CONCLUSIONS: Adjuvant chemotherapy should be recommended for patients with surgically treated PSC, especially for patients with advanced-stage cancer, younger age, or higher body mass index.


Assuntos
Carcinoma/tratamento farmacológico , Carcinoma/cirurgia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/cirurgia , Sarcoma/tratamento farmacológico , Sarcoma/cirurgia , Idoso , Quimioterapia Adjuvante , China , Feminino , Hospitais Especializados , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Programa de SEER
20.
Eur J Cancer ; 130: 182-192, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32224416

RESUMO

PURPOSE: This is a first-in-human phase I study investigating the safety and efficacy of toripalimab, a humanized monoclonal antibody against the programmed cell death-1 (PD-1) receptor, in Chinese patients with advanced or recurrent malignant tumor refractory to standard treatment. PATIENTS AND METHODS: During dose escalation, patients received a single-dose intravenous infusion of toripalimab for 56 days followed by multidose infusions every two weeks. The planned dosing groups were 1, 3 and 10 mg/kg. During dose expansion, patients received toripalimab every two weeks. Clinical response was evaluated by investigators every 6 weeks. RESULTS: Thirty-three patients were enrolled, including 12 patients with alveolar soft part sarcoma (ASPS), seven with non-small-cell lung cancer and 11 with lymphoma. Patients were heavily pretreated with a median of 3 prior lines of systemic treatments. Toripalimab was well tolerated without dose-limiting toxicity. All patients experienced treatment-related adverse events. Grade 3 and above treatment-related adverse events occurred in six (18.2%) patients. Among 22 solid tumors, the objective response rate (ORR) was 22.7% per RECIST v1.1. The ORR was 90.9% in 11 lymphoma patients per IWG 2007. The median duration of response was 21.5 months. The median progression-free survival was 5.7 months for solid tumors and 8.3 months for lymphomas. The median OS was not reached for all patients and the lymphoma subgroups. The median OS was 34.7 months for patients with ASPS. CONCLUSION: Toripalimab was well tolerated up to 10 mg/kg Q2W without dose-limiting toxicity and showed promising and durable antitumour activities in patients with ASPS and lymphoma, who were heavily pretreated. CLINICAL TRIAL INFORMATION: ClinicalTrials.gov Identifier: NCT02836834.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Carcinoma/tratamento farmacológico , Imunoterapia/métodos , Receptor de Morte Celular Programada 1/uso terapêutico , Adulto , Idoso , Anticorpos Monoclonais Humanizados/farmacologia , Carcinoma/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...