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1.
World J Surg Oncol ; 19(1): 205, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34238296

RESUMO

PURPOSE: To assess the value of adjuvant radiotherapy for treatment of gastric adenocarcinoma and to investigate subgroups of patients suitable for adjuvant radiotherapy. METHODS AND MATERIALS: Data from 785 patients with gastric adenocarcinoma who had undergone D1/D2 radical resection and adjuvant chemotherapy were collected, the site of first progression was determined, and the relationship between the rate of local recurrence and clinicopathologic features was analyzed. RESULTS: By the end of the follow-up period, progression was observed in 405 patients. Local recurrence was observed as the first progression in 161 cases. The local recurrence rate was significantly lower than the non-local progression rate (20.5% vs 31.5%, p=0.007). Multivariate Cox regression analysis showed a significant relationship among degree of differentiation, T stage, N stage, and rate of local recurrence. CONCLUSIONS: Not all patients with gastric carcinoma required adjuvant radiotherapy. However, patients with poorly differentiated cancer cells, advanced T stage (T3/T4), and positive lymph nodes, which included patients in the T4N1-2M0 subgroup, were recommended for adjuvant radiotherapy.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/radioterapia , Quimioterapia Adjuvante , Gastrectomia , Humanos , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/radioterapia
2.
S D Med ; 74(3): 128-130, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34232592

RESUMO

The concurrence of two histologically different primary malignancies is rare and diagnostically challenging. Management and monitoring for progression also add to the dilemma as management varies amongst various types of malignancies and radiological imaging cannot differentiate between different primaries. We present a case of 62-year-old male with history of invasive squamous cell carcinoma of chest wall who was found to have cavitary lesions on a chest CT. Initially thought to be metastatic, as squamous cell carcinoma is notorious to case cavitary lesions, on biopsy they turned out be a separate primary malignancy, i.e. adenocarcinoma of the lung. The case highlights, not only such a possibility, but also the need of research to find common chemotherapeutic drugs that can target both pathologies and save patients from side effects of additional anticancer therapies.


Assuntos
Adenocarcinoma , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Parede Torácica , Adenocarcinoma/tratamento farmacológico , Carcinoma de Células Escamosas/diagnóstico por imagem , Humanos , Pulmão , Masculino , Pessoa de Meia-Idade , Parede Torácica/diagnóstico por imagem
3.
BMC Gastroenterol ; 21(1): 284, 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34247571

RESUMO

BACKGROUND: Gastrointestinal adenocarcinoma (GIAD) has caused a serious disease burden globally. Targeted therapy for the transforming growth factor beta (TGF-ß) signaling pathway is becoming a reality. However, the molecular characterization of TGF-ß associated signatures in GIAD requires further exploration. METHODS: Multi-omics data were collected from TCGA and GEO database. A pivotal unsupervised clustering for TGF-ß level was performed by distinguish status of TGF-ß associated genes. We analyzed differential mRNAs, miRNAs, proteins gene mutations and copy number variations in both clusters for comparison. Enrichment of pathways and gene sets were identified in each type of GIAD. Then we performed differential mRNA related drug response by collecting data from GDSC. At last, a summarized deep neural network for TGF-ß status and GIADs was constracted. RESULTS: The TGF-ßhigh group had a worse prognosis in overall GIAD patients, and had a worse prognosis trend in gastric cancer and colon cancer specifically. Signatures (including mRNA and proteins) of the TGF-ßhigh group is highly correlated with EMT. According to miRNA analysis, miR-215-3p, miR-378a-5p, and miR-194-3p may block the effect of TGF-ß. Further genomic analysis showed that TGF-ßlow group had more genomic changes in gastric cancer, such as TP53 mutation, EGFR amplification, and SMAD4 deletion. And drug response dataset revealed tumor-sensitive or tumor-resistant drugs corresponding to TGF-ß associated mRNAs. Finally, the DNN model showed an excellent predictive effect in predicting TGF-ß status in different GIAD datasets. CONCLUSIONS: We provide molecular signatures associated with different levels of TGF-ß to deepen the understanding of the role of TGF-ß in GIAD and provide potential drug possibilities for therapeutic targets in different levels of TGF-ß in GIAD.


Assuntos
Adenocarcinoma , MicroRNAs , Preparações Farmacêuticas , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Variações do Número de Cópias de DNA , Humanos , MicroRNAs/genética , Fator de Crescimento Transformador beta/genética
4.
Gan To Kagaku Ryoho ; 48(7): 979-982, 2021 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-34267041

RESUMO

A 75-year-old woman was treated with TC plus Bev for cancer of unknown primary. During treatment, she presented to the clinic with chief complaints of general malaise and anorexia. On presentation, abdominal distention and upper abdominal tenderness were noted, and sepsis was suspected. A thoracoabdominal CT scan revealed prominent intramural emphysema and mesenteric gas in the ascending colon. An emergency laparotomy was performed for suspected pneumatosis intestinalis non-obstructive intestinal ischemia. However, no intra-abdominal contamination or ischemic changes were observed intraoperatively. Histological examination revealed a small adenocarcinoma on the serous surface of the ascending colon, and immunochemical staining confirmed the diagnosis of serous adenocarcinoma as the patient's primary cancer. This report describes a case in which the patient achieved long-term survival after diagnosis. It also emphasizes the importance of identifying the subset of patients with cancer of unknown primary who have a good prognosis in order to provide appropriate treatment.


Assuntos
Adenocarcinoma , Neoplasias Primárias Desconhecidas , Pneumatose Cistoide Intestinal , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Idoso , Bevacizumab , Feminino , Humanos , Laparotomia , Neoplasias Primárias Desconhecidas/tratamento farmacológico , Pneumatose Cistoide Intestinal/induzido quimicamente , Pneumatose Cistoide Intestinal/diagnóstico por imagem
6.
Magy Onkol ; 65(2): 103-111, 2021 Jun 03.
Artigo em Húngaro | MEDLINE | ID: mdl-34081758

RESUMO

The therapeutic impact of KRAS mutations remains controversial in bone metastatic lung adenocarcinoma (LADC). Therefore, our aim was to investigate the effects of KRAS mutational status on overall survival (OS) in these patients according to bisphosphonate therapy (BTx) and radiation therapy (RTx). In total, 134 LADC patients diagnosed with simultaneous bone metastasis were included in this study. The results of the univariate (p=0.008) and multivariate (p=0.004) survival analyses indicated that KRAS mutation is a negative prognostic factor. Both BTx and RTx can increase the OS with a pronounced benefit for patients with KRAS wild-type tumors. Importantly, the concomitant use of BTx and RTx might increase the OS irrespective of KRAS status compared to BTx or RTx alone. In summary, our results might contribute to the development of new therapeutic approaches with regards to KRAS mutational status in bone metastatic LADC.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Colorretais , Neoplasias Pulmonares , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Difosfonatos/uso terapêutico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Prognóstico , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas ras/genética
7.
Int J Mol Sci ; 22(11)2021 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-34071152

RESUMO

Prostate cancer (PCa) is the second most common cancer in men, causing more than 300,000 deaths every year worldwide. Due to their superior cell-killing ability and the relative simplicity of their preparation, immunotoxin molecules have great potential in the clinical treatment of cancer, and several such molecules have been approved for clinical application. In this study, we adopted a relatively simple strategy based on a single-domain antibody (sdAb) and an improved Pseudomonas exotoxin A (PE) toxin (PE24X7) to prepare a safer immunotoxin against prostate-specific membrane antigen (PSMA) for PCa treatment. The designed anti-PSMA immunotoxin, JVM-PE24X7, was conveniently prepared in its soluble form in an Escherichia coli (E. coli) system, avoiding the complex renaturation process needed for immunotoxin preparation by the conventional strategy. The product was very stable and showed a very strong ability to bind the PSMA receptor. Cytotoxicity assays showed that this molecule at a very low concentration could kill PSMA-positive PCa cells, with an EC50 value (concentration at which the cell viability decreased by 50%) of 15.3 pM against PSMA-positive LNCaP cells. Moreover, this molecule showed very good killing selectivity between PSMA-positive and PSMA-negative cells, with a selection ratio of more than 300-fold. Animal studies showed that this molecule at a very low dosage (5 × 0.5 mg/kg once every three days) completely inhibited the growth of PCa tumors, and the maximum tolerable dose (MTD) was more than 15 mg/kg, indicating its very potent tumor-treatment ability and a wide therapeutic window. Use of the new PE toxin, PE24X7, as the effector moiety significantly reduced off-target toxicity and improved the therapeutic window of the immunotoxin. The above results demonstrate that the designed anti-PSMA immunotoxin, JVM-PE24X7, has good application value for the treatment of PCa.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antígenos de Neoplasias/imunologia , Antineoplásicos Imunológicos/uso terapêutico , Glutamato Carboxipeptidase II/antagonistas & inibidores , Imunotoxinas/uso terapêutico , Terapia de Alvo Molecular , Neoplasias da Próstata/tratamento farmacológico , Anticorpos de Domínio Único/uso terapêutico , Animais , Especificidade de Anticorpos , Reações Antígeno-Anticorpo , Antígenos de Superfície/imunologia , Antineoplásicos Imunológicos/toxicidade , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Glutamato Carboxipeptidase II/imunologia , Humanos , Imunotoxinas/toxicidade , Masculino , Dose Máxima Tolerável , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Modelos Moleculares , Conformação Proteica , Proteínas Recombinantes de Fusão/uso terapêutico , Proteínas Recombinantes de Fusão/toxicidade , Anticorpos de Domínio Único/toxicidade , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Rev Med Liege ; 76(5-6): 515-518, 2021 May.
Artigo em Francês | MEDLINE | ID: mdl-34080389

RESUMO

Currently, the standard management of locally advanced adenocarcinoma of the middle and lower rectum consists in first intention of pre-operative radio-chemotherapy. This treatment is then usually followed by rectal surgery with removal of the mesorectum. The local recurrence rate is quite low, but at the cost of a non negligible morbidity (urinary, anal and sexual functional sequelae). This raises the question of a possible sparing of surgery and therefore organ preservation in well selected patients with a complete response after radio-chemotherapy. The Brazilians are pioneers in this field. Already in 2004, their publications suggested that the «Watch and Wait¼ strategy was safe and effective in patients with a complete clinical response. Other publications have followed and tend to confirm that there is no oncological risk in proposing a «watch and wait¼ strategy for these well selected patients in complete clinical, endoscopic and iconographic remission on the basis of magnetic resonance imaging (MRI). In these conditions, an attentive surveillance strategy allows to avoid operative morbi-mortality without oncological compromise. Monitoring is therefore multi-modal, clinical and endoscopic, but also based on MRI.


Assuntos
Adenocarcinoma , Neoplasias Retais , Adenocarcinoma/tratamento farmacológico , Quimiorradioterapia , Humanos , Terapia Neoadjuvante , Recidiva Local de Neoplasia , Neoplasias Retais/terapia , Resultado do Tratamento , Conduta Expectante
9.
Medicine (Baltimore) ; 100(19): e25773, 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34106609

RESUMO

RATIONALE: Anti-PD-1 antibody is the standard therapy for treatment-resistant gastric cancer, but only a limited number of patients respond. Additionally, cases of hyper-progressive disease (HPD) in which tumor growth accelerates after anti-PD-1 antibody administration have been reported; however, the biological mechanism has not been elucidated. PATIENT CONCERNS: In the present case, metastatic gastric cancer was treated with the anti-PD-1 antibody, nivolumab, as third-line treatment. DIAGNOSIS: After the initiation of nivolumab therapy, a rapidly enlarging para-aortic lymph nodes were observed leading to the diagnosis of HPD. INTERVENTIONS: Multiplex immunohistochemistry was used to examine immune cells infiltrating in the primary tumor and in liver metastasis which were obtained before nivolumab treatment, and in lymph node metastasis which presented with HPD after nivolumab therapy. OUTCOMES: In the primary tumor, helper T (Th) cells, cytotoxic T lymphocytes (CTLs), regulatory T (Treg) cells, and PD-L1-negative macrophages were observed. On the other hand, in metastatic lymph nodes presenting with HPD, PD-L1-positive macrophages prominently increased, while Treg cells, CTLs, and Th cells decreased. PD-L1 expression was not observed in gastric cancer cells among the three specimens. LESSONS: The findings suggest the possibility that PD-L1-positive M2 macrophage might contribute to acceleration of tumor growth with anti-PD-1 therapy in the present case.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos Imunológicos/efeitos adversos , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Nivolumabe/efeitos adversos , Neoplasias Gástricas/tratamento farmacológico , Macrófagos Associados a Tumor/efeitos dos fármacos , Adenocarcinoma/imunologia , Adenocarcinoma/patologia , Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Biomarcadores Tumorais/antagonistas & inibidores , Progressão da Doença , Evolução Fatal , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Nivolumabe/uso terapêutico , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/patologia , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/patologia
10.
In Vivo ; 35(4): 2297-2303, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34182509

RESUMO

BACKGROUND/AIM: Cervical oesophageal adenocarcinoma (COA) is extremely rare. We present a case of human epidermal growth factor receptor 2 (HER2)-positive COA that showed repeated recurrences despite multidisciplinary treatments. CASE REPORT: A 49-year-old male was diagnosed with clinical stage IVA COA that originated from ectopic gastric mucosa. He initially underwent definitive chemoradiotherapy (CRT) (60.0 Gy/30 fractions, 5-fluorouracil, and cisplatin). Two months after CRT, the right supraclavicular lymph node (LN) reenlarged and salvage lymphadenectomy was performed. Immunohistochemical staining revealed a HER2-positive adenocarcinoma. Four months after lymphadenectomy, multiple metastases in the mediastinal LNs and lungs were detected, and S-1, oxaliplatin and trastuzumab were administered. Four months after chemotherapy, the patient presented with new liver metastasis. Further metastasis was prevented by Nivolumab treatment for four months. CONCLUSION: HER2-positive COA may be more aggressive and may require further intensive treatments. This literature review may be helpful in determining treatment strategies for COA.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Adenocarcinoma/diagnóstico , Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/uso terapêutico , Esôfago , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Receptor ErbB-2/genética , Neoplasias Gástricas/tratamento farmacológico
11.
BMC Gastroenterol ; 21(1): 270, 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34187383

RESUMO

BACKGROUND: Tumor-to-tumor metastasis is the rare phenomenon in which one tumor exhibits metastatic deposits from another. To the best of our knowledge, there has been no prior reported case of tumor-to-tumor metastasis of a diffuse large B cell lymphoma (DLBCL) to a primary gastric adenocarcinoma. CASE PRESENTATION: A 70-year-old man presented with chest discomfort. An echocardiogram showed the presence of a right ventricular tumor. A positron emission tomogram showed multiple foci of abnormal activity in right cervical lymph nodes, cardiac wall, and stomach. A right cervical lymph node biopsy specimen revealed histological features of DLBCL. An esophagogastroduodenoscopy showed a large circumferential ulceration on the gastric body. Subsequent biopsy revealed adenocarcinoma cells surrounded by infiltrating lymphoma cells. On immunohistochemical staining, lymphoma cells were positive for CXCR4 and adenocarcinoma cells were positive for CXCL12/SDF-1. The patient was treated with six cycles of R-CHOP chemotherapy regimen, resulting in a complete remission. CONCLUSIONS: This patient's case implies that the interaction between a chemokine and its receptor may be the underlying mechanism for the observed tumor-to-tumor metastasis. Specifically, our case would suggest an involvement of the CXCL12 (SDF-1)/CXCR4 axis in the observed metastasis of DLBCL to primary gastric adenocarcinoma.


Assuntos
Adenocarcinoma , Linfoma Difuso de Grandes Células B , Neoplasias Gástricas , Adenocarcinoma/tratamento farmacológico , Idoso , Quimiocina CXCL12 , Humanos , Linfonodos , Metástase Linfática , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Masculino , Receptores CXCR4 , Neoplasias Gástricas/tratamento farmacológico
12.
J Food Biochem ; 45(6): e13760, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33974285

RESUMO

Andean Berry (Vaccinium meridionale Sw.) is a South American fruit rich in phytochemicals with promising anti-cancer properties as co-adjuvants to nonsteroidal anti-inflammatory drugs such as Aspirin. This study aimed to evaluate the antiproliferative potential of Andean Berry Juice (ABJ) in combination with Aspirin in human SW480 colon adenocarcinoma cells. ABJ primarily contained 3,4-dihydroxybenzoic and chlorogenic acids. The combined treatment of ABJ (IC50 : 30.0 ± 0.11%) and Aspirin (IC50 : 20.0 ± 0.57) exhibited a higher (p < .01) antiproliferative effect than each counterpart. Moreover the same mixture displayed a lower reduced glutathione/oxidized glutathione ratio (GSH/GSSG) than the untreated cells. ABJ-Aspirin combination induced late apoptosis stage without stimulating mitochondrial depolarization and prompted phosphatidylserine relocalization. These results emphasize the antiproliferative potential of bioactive compounds from ABJ and Aspirin combinations. PRACTICAL APPLICATIONS: Natural products such as Andean Berry (V. meridionale Sw.) juice (ABJ) contains antioxidant polyphenols that could reduce the need to use non-steroidal anti-inflammatory drugs, currently employed in cancer treatment, to prevent its side effects. The high abundance of polyphenols from this underutilized berry could stimulate the standardization of its production and industrial exploitation to be transformed into suitable food products delivering natural bioactive compounds with potential anti-cancer effects in vitro.


Assuntos
Adenocarcinoma , Vaccinium , Adenocarcinoma/tratamento farmacológico , Aspirina , Colo , Frutas , Humanos
13.
Nat Commun ; 12(1): 2581, 2021 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-33972544

RESUMO

While the potential of patient-derived organoids (PDOs) to predict patients' responses to anti-cancer treatments has been well recognized, the lengthy time and the low efficiency in establishing PDOs hamper the implementation of PDO-based drug sensitivity tests in clinics. We first adapt a mechanical sample processing method to generate lung cancer organoids (LCOs) from surgically resected and biopsy tumor tissues. The LCOs recapitulate the histological and genetic features of the parental tumors and have the potential to expand indefinitely. By employing an integrated superhydrophobic microwell array chip (InSMAR-chip), we demonstrate hundreds of LCOs, a number that can be generated from most of the samples at passage 0, are sufficient to produce clinically meaningful drug responses within a week. The results prove our one-week drug tests are in good agreement with patient-derived xenografts, genetic mutations of tumors, and clinical outcomes. The LCO model coupled with the microwell device provides a technically feasible means for predicting patient-specific drug responses in clinical settings.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Técnicas de Cultura de Células/métodos , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Neoplasias Pulmonares/tratamento farmacológico , Organoides/efeitos dos fármacos , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Animais , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais/instrumentação , Gefitinibe/farmacologia , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos NOD , Organoides/citologia , Organoides/patologia , Preparações Farmacêuticas , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Gan To Kagaku Ryoho ; 48(5): 685-687, 2021 May.
Artigo em Japonês | MEDLINE | ID: mdl-34006714

RESUMO

A 73‒year‒old woman underwent right lower lobectomy for Stage ⅠA(pathological Stage T1N0M0)pulmonary adenocarcinoma. After 19 years, she complained of dyspnea on exertion. Computed tomography revealed metastatic lesions in the bilateral supraclavicular, mediastinal, and hilar lymph nodes. Thoracoscopic lymph node biopsy showed recurrence of the adenocarcinoma, and immunohistochemical staining confirmed that the metastases were ROS1‒positive. The patient responded well to crizotinib therapy. The prognosis of non‒small‒cell lung cancer is considered favorable when it does not recur within 5 years, postoperation. However, few studies have reported the recurrence of ROS1‒positive pulmonary adenocarcinoma after a long disease‒free interval. Long‒term postoperative follow‒up is essential for patients with ROS1‒positive pulmonary adenocarcinomas.


Assuntos
Adenocarcinoma , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Idoso , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/cirurgia , Linfonodos , Recidiva Local de Neoplasia , Proteínas Tirosina Quinases , Proteínas Proto-Oncogênicas
15.
World J Gastroenterol ; 27(17): 1847-1863, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-34007126

RESUMO

Pancreatic cancer is considered one of the most aggressive cancers, with an increasing incidence in recent years. To date, chemotherapy is still the standard of care for advanced metastatic disease, unfortunately providing only a slight advantage in terms of survival. The molecular and cellular characteristics of pancreatic cancer cells, as well as the cells that characterize the pancreatic tumour microenvironment, are the basis of the mechanisms of resistance to treatment. After progression during first-line treatment, few patients are eligible for second-line treatment due to the loss of performance status. To date, a clear survival advantage has not yet been demonstrated for second-line chemotherapy. Precision medicine could be the key to increasing responses to cancer treatment and finally impacting survival in this difficult-to-treat disease. In this review, we analyze current recommendations in the second-line setting and potential future prospects.


Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Microambiente Tumoral
16.
BMJ Case Rep ; 14(5)2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33947675

RESUMO

Radiation recall (RR) is a chemotherapy-induced reaction that leads to inflammation and necrosis in previously irradiated tissue. Gemcitabine is a cytidine analogue that is often used in conjunction with nab-paclitaxel in the treatment of pancreatic cancer. Herein, we present a case of a 56-year-old woman with stage III pancreatic adenocarcinoma diagnosed with gemcitabine-induced RR when she presented with lower back pain and new rim-enhancing collections within the right and left paraspinal musculature 5 months after radiation therapy to the pancreas. A PubMed search was performed for 'Radiation Recall Myositis' and a complete literature review performed. This case and review of the literature of published cases of RR myositis highlight the clinical course and presentation of RR myositis. This review highlights the importance of considering RR in the differential diagnosis when patients who are undergoing chemotherapy and radiation present with inflammatory changes in previously irradiated areas.


Assuntos
Adenocarcinoma , Miosite , Neoplasias Pancreáticas , Adenocarcinoma/tratamento farmacológico , Albuminas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Feminino , Humanos , Pessoa de Meia-Idade , Miosite/induzido quimicamente , Miosite/diagnóstico , Paclitaxel/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico
17.
Medicine (Baltimore) ; 100(21): e26068, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34032736

RESUMO

ABSTRACT: Some patients with advanced colon adenocarcinoma (COAD) are not sensitive to radiotherapy and chemotherapy, and as such, immunotherapy has become the most popular option for these patients. However, different patients respond differently to immunotherapy. Tumor mutational burden (TMB) has been used as a predictor of the response of advanced COAD patients to immunotherapy. A high TMB typically indicates that the patient's immune system will respond well to immunotherapy. In addition, while microRNAs (miRNA) have been shown to play an important role in treatment responses associated with the immune system, the relationship between miRNA expression levels and TMB has not been clarified in COAD.We downloaded miRNA data and mutational files of COAD from the Cancer Genome Atlas database. Differentially expressed miRNAs were screened in the training group, and miRNAs used to construct the model were further identified using the LASSO logistic regression method. After building the miRNA-based model, we explored the correlation between the model and TMB. The model was verified by a receiver operating characteristic curve, and the correlation between it and 3 widely used immune checkpoints (programmed death receptor-1, programmed death-ligand 1, and cytotoxic T-lymphocyte associated protein-4) was explored. Functional enrichment analysis of the selected miRNAs was performed, and these respective miRNA target genes were predicted using online tools.Our results showed that a total of 32 differentially expressed miRNAs were used in the construction of the model. The accuracies of the models of the 2 datasets (training and test sets) were 0.987 and 0.934, respectively. Correlation analysis showed that the correlation of the model with programmed death-ligand 1 and cytotoxic T-lymphocyte associated protein-4, as well as TMB, was high, but there was no correlation with programmed death receptor-1. The results of functional enrichment analysis indicated that these 32 miRNAs were involved in many immune-related biological processes and tumor-related pathways.Therefore, this study demonstrated that differentially expressed miRNAs can be used to predict the TMB level, which can help identify advanced COAD patients who will respond well to immunotherapy. The miRNA-based model may be used as a tool to predict the TMB level in patients with advanced COAD.


Assuntos
Adenocarcinoma/genética , Biomarcadores Tumorais/metabolismo , Neoplasias do Colo/genética , MicroRNAs/metabolismo , Modelos Genéticos , Adenocarcinoma/diagnóstico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Idoso , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/análise , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Análise Mutacional de DNA , Conjuntos de Dados como Assunto , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Modelos Logísticos , Masculino , MicroRNAs/análise , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Curva ROC , Tolerância a Radiação/genética
18.
Medicine (Baltimore) ; 100(21): e26146, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34032767

RESUMO

RATIONALE: Hormone therapies, particularly those targeting estrogen and its receptors, are a key treatment modality for patients with estrogen receptor (ER)-positive breast or ovarian cancer. Some gastric cancers (GCs) express ERs, and preclinical studies suggest the potential of estrogen-targeting hormone therapy on GC; however, the clinical relevance of this hormone therapy on GC treatment has not been well elucidated. PATIENT CONCERNS: An 80-year-old female was admitted to our department with hypogastric pain and vomiting. Computed tomography demonstrated small bowel obstruction, and laparotomy after bowel decompression revealed peritoneal dissemination consisting of a poorly-differentiated adenocarcinoma. Intestinal bypass between the ileum and transverse colon was performed. DIAGNOSES: The tumor was ER- and mammaglobin-positive, indicating that it originated from a breast cancer. Diagnostic imaging revealed no evidence of breast cancer; however, right axillary ER- and mammaglobin-positive lymphadenopathy was found. INTERVENTIONS: The patient received hormone therapy using letrozole based on a clinical diagnosis of occult breast cancer with peritoneal dissemination and right axillary lymph node metastasis. OUTCOMES: The patient remained disease free until 37 months but deceased at 53 months from the onset of disease. An autopsy revealed no tumor cells in the right breast tissue; however, there was a massive invasion of cancer cells in the stomach. LESSONS: A patient with ER positive GC with peritoneal dissemination and right axillary lymph node metastasis presented remarkable response to letrozole. The long-term survival obtained using letrozole for a patient with GC with distant metastasis suggests the potential of estrogen targeting hormone therapies for GC.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Letrozol/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/patologia , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Evolução Fatal , Feminino , Humanos , Metástase Linfática , Receptores de Estrogênio/análise , Neoplasias Gástricas/secundário
19.
J Vis Exp ; (170)2021 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-33999032

RESUMO

Patient-derived organoid (PDO) models allow for long-term expansion and maintenance of primary epithelial cells grown in three dimensions and a near-native state. When derived from resected or biopsied tumor tissue, organoids closely recapitulate in vivo tumor morphology and can be used to study therapy response in vitro. Biobanks of tumor organoids reflect the vast variety of clinical tumors and patients and therefore hold great promise for preclinical and clinical applications. This paper presents a method for medium-throughput drug screening using head and neck squamous cell carcinoma and colorectal adenocarcinoma organoids. This approach can easily be adopted for use with any tissue-derived organoid model, both normal and diseased. Methods are described for in vitro exposure of organoids to chemo- and radiotherapy (either as single-treatment modality or in combination). Cell survival after 5 days of drug exposure is assessed by measuring adenosine triphosphate (ATP) levels. Drug sensitivity is measured by the half-maximal inhibitory concentration (IC50), area under the curve (AUC), and growth rate (GR) metrics. These parameters can provide insight into whether an organoid culture is deemed sensitive or resistant to a particular treatment.


Assuntos
Adenocarcinoma , Antineoplásicos/farmacologia , Neoplasias Colorretais , Avaliação Pré-Clínica de Medicamentos/métodos , Neoplasias de Cabeça e Pescoço , Organoides/efeitos dos fármacos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/radioterapia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/radioterapia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Técnicas de Cultura de Órgãos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia
20.
Cancer Treat Rev ; 98: 102219, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33993033

RESUMO

With an incidence that is constantly rising, oesophageal adenocarcinoma (OAC) is becoming an increasing health burden worldwide. Although significant advances in treatment regimens have improved patient outcomes, survival rates for this deadly cancer remain unsatisfactory. This highlights the need to improve current therapeutic approaches and develop novel therapeutic strategies for treating OAC patients. The advent of immunotherapy has revolutionised treatment across a range of malignancies, however outcomes in OAC show modest results. The inherent resistance of OAC to treatment reflects the complex genomic landscape of this cancer, which displays a lack of ubiquitous driver mutations and large-scale genomic alterations along with high tumour and immune heterogeneity. Research into the immune landscape of OAC is limited, and elucidation of the mechanisms surrounding the immune responses to this complex cancer will result in improved therapeutic approaches. This review explores what is known about the immuno-biology of OAC and explores promising therapeutic avenues that may improve responses to immunotherapeutic regimens.


Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/imunologia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/imunologia , Imunoterapia/métodos , Adenocarcinoma/patologia , Animais , Neoplasias Esofágicas/patologia , Humanos
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