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1.
Gene ; 932: 148900, 2025 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-39209180

RESUMO

Gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide because of its high morbidity and the absence of effective therapies. Even though paclitaxel is a powerful anticancer chemotherapy drug, recent studies have indicated its ineffectiveness against GC cells. Long non-coding RNA (lncRNA) PVT1 has a high expression in GC cells and increases the progression of tumors via inducing drug resistance. In the present study, the effects of the siRNA-mediated lncRNA PVT1 gene silencing along with paclitaxel treatment on the rate of apoptosis, growth, and migration of AGS GC cells were investigated. AGS cells were cultured and then transfected with siRNA PVT1 using electroporation. The MTT test was used to examine the effect of treatments on the viability of cultured cells. Furthermore, the flow cytometry method was used to evaluate the impact of treatments on the cell cycle process and apoptosis induction in GC cells. Finally, the mRNA expression of target genes was assessed using the qRT-PCR method. The results showed that lncRNA PVT1 gene suppression, along with paclitaxel treatment, reduces the viability of cancer cells and significantly increases the apoptosis rate of cancer cells and the number of cells arrested in the G2/M phase compared to the control group. Based on the results of qRT-PCR, combined treatment significantly decreased the expression of MMP3, MMP9, MDR1, MRP1, Bcl-2, k-Ras, and c-Myc genes and increased the expression of the Bax gene compared to the control group. The results of our study showed that lncRNA PVT1 gene targeting, together with paclitaxel treatment, induces apoptosis, inhibits growth, alleviates drug resistance, and reduces the migratory capability of GC cells. Therefore, there is a need for further investigations to evaluate the feasibility and effectiveness of this approach in vivo in animal models.


Assuntos
Apoptose , Resistencia a Medicamentos Antineoplásicos , Inativação Gênica , Paclitaxel , RNA Longo não Codificante , Neoplasias Gástricas , RNA Longo não Codificante/genética , Paclitaxel/farmacologia , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Apoptose/genética , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Antineoplásicos Fitogênicos/farmacologia , RNA Interferente Pequeno/genética
2.
Biomaterials ; 312: 122740, 2025 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39096839

RESUMO

Metastasis stands as the primary contributor to mortality associated with tumors. Chemotherapy and immunotherapy are frequently utilized in the management of metastatic solid tumors. Nevertheless, these therapeutic modalities are linked to serious adverse effects and limited effectiveness in preventing metastasis. Here, we report a novel therapeutic strategy named starvation-immunotherapy, wherein an immune checkpoint inhibitor is combined with an ultra-long-acting L-asparaginase that is a fusion protein comprising L-asparaginase (ASNase) and an elastin-like polypeptide (ELP), termed ASNase-ELP. ASNase-ELP's thermosensitivity enables it to generate an in-situ depot following an intratumoral injection, yielding increased dose tolerance, improved pharmacokinetics, sustained release, optimized biodistribution, and augmented tumor retention compared to free ASNase. As a result, in murine models of oral cancer, melanoma, and cervical cancer, the antitumor efficacy of ASNase-ELP by selectively and sustainably depleting L-asparagine essential for tumor cell survival was substantially superior to that of ASNase or Cisplatin, a first-line anti-solid tumor medicine, without any observable adverse effects. Furthermore, the combination of ASNase-ELP and an immune checkpoint inhibitor was more effective than either therapy alone in impeding melanoma metastasis. Overall, the synergistic strategy of starvation-immunotherapy holds excellent promise in reshaping the therapeutic landscape of refractory metastatic tumors and offering a new alternative for next-generation oncology treatments.


Assuntos
Asparaginase , Inibidores de Checkpoint Imunológico , Imunoterapia , Animais , Asparaginase/uso terapêutico , Asparaginase/farmacologia , Asparaginase/química , Imunoterapia/métodos , Feminino , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Camundongos , Humanos , Linhagem Celular Tumoral , Sinergismo Farmacológico , Elastina/química , Elastina/metabolismo , Metástase Neoplásica , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos BALB C , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Distribuição Tecidual
3.
Cancer Rep (Hoboken) ; 7(9): e70003, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39233667

RESUMO

BACKGROUND: The bone is among the most frequently chosen sites for the metastatic spread of breast cancer. The prediction of biomarkers for BM (Bone Metastasis) and PDB (Paget's disease of bone) initiated from breast cancer could be critically important in categorizing individuals with a higher risk and providing targeted treatment for PDB and BM. AIMS: This research aims to investigate the common key candidate biomarkers that contribute to BM-BCa (Bone metastasis of breast cancer) and PDB by employing network decomposition and functional enrichment studies. METHODS AND RESULTS: This research analyzed high-throughput transcriptome sequencing (RNA-Seq). For this work, the dataset (GSE121677) was downloaded from GEO (Gene Expression Omnibus), and DEGs were identified using Galaxy and R script 4.3. Using STRING (Search Tool for the Retrieval of Interacting Genes), high-throughput research created a protein-protein interaction network (PPIN). The BM-PDB-interactome was created using Cytoscape 3.9.1 and PDB biomarkers, with the top 3% DEGs from BM-BCa. Functional Enrichment Analysis (Funrich 3.1.3) and DAVID 6.8 performed functional and gene set enrichment analysis (GSEA) of putatively essential biomarkers. TCGA (The Cancer Genome Atlas) validated the discovered genes. Based on our research, we identified 1262 DEGs; among these DEGs, 431 genes were upregulated, and 831 genes were downregulated. During the third growth of the interactome, 20 more genes were pinned to the BM-PDB interactome. RAC2, PIAS1, EP300, EIF2S1, and LRP6 are among the additional 25% of genes identified to interact with the BM-PDB interactome. To corroborate the findings of the research presented, additional functional and gene set enrichment analyses have been performed. CONCLUSION: Of the five reported genes (RAC2, PIAS1, EP300, EIF2S1, and LRP6), RAC2 was identified to function as the common key potential biomarker in the BM-PDB interactome analysis and validated by TCGA in the study presented.


Assuntos
Biomarcadores Tumorais , Neoplasias Ósseas , Neoplasias da Mama , Osteíte Deformante , Mapas de Interação de Proteínas , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Feminino , Neoplasias Ósseas/secundário , Neoplasias Ósseas/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Osteíte Deformante/genética , Osteíte Deformante/patologia , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Transcriptoma , Sequenciamento de Nucleotídeos em Larga Escala
4.
Oncol Lett ; 28(5): 500, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39233821

RESUMO

Low-grade appendiceal mucinous neoplasm (LAMN) is a tumor that primarily originates from the appendix and belongs to the family of appendiceal mucinous neoplasms (AMNs). In 50% of female patients, AMNs (particularly LAMNs) have a tendency to metastasize to organs in the genital tract, where the neoplasm can mimic the features of primary ovarian mucinous cancer (POMC). The present case report reviewed the difficulties in differentiating between these two types of tumors. In the present case report, a 61-year-old female patient was admitted to the Second Department of Gynecological Surgery and Gynecological Oncology, University Clinical Hospital no. 4 at Lublin Medical University (Lublin, Poland) with the diagnosis of a right ovarian mass. After performing ultrasound and computed tomography (CT) scans and laboratory analysis, the patient underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, appendectomy and resection of the Douglas peritoneum. Notably, the postoperative pathological assessment revealed LAMN with metastases to the right ovary and omentum. Immunohistochemically, cytokeratin 20 and caudal type homeobox 2 both stained positively, whereas paired box gene 8 stained negatively. After surgery, the patient received the recommended hyperthermic intraperitoneal chemotherapy at the Department of Surgical Oncology at Lublin Medical University. After 1 year, a CT scan was performed, which indicated no evidence of recurrent disease. In conclusion, observations from the present case report suggest that gynecologists should be conscious of the possibility of malignancies of gastrointestinal origin in cases of ovarian tumors instead of making direct assumptions of POMC. If the mucinous mass involves the base of the appendix or if there is a suspicion of positive margins, then cytoreductive surgery and right-sided hemicolectomy must be performed. In addition, identifying the origin of mucinous tumors in the right ovary and/or the appendix requires the histopathological examination of a panel of markers using immunohistochemistry.

5.
Natl J Maxillofac Surg ; 15(2): 199-207, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39234138

RESUMO

Distant metastasis to salivary glands is a very rare event and most often associated with primary malignancies of the skin. Only 1-4% of all salivary gland tumours manifest with metastasis. Carcinomas of the breast, lung, kidney and prostate are those primaries that may also potentially metastasize to salivary glands. Literature has documented several studies analysing metastatic tumours in the oral region. However, very little research work has been published to date to analyse solely the Breast cancer metastasizing to the salivary glands. Thus, this review was conducted to examine the published cases of Breast cancer metastasizing to salivary glands from March 1975 to March 2023. An electronic search of the published literature was performed without publication year limitation in PubMed/ Medline, Scopus, Google Scholar, Web of Science, Science Direct, Embase, and Research Gate databases, using mesh keywords like ('Breast cancer' OR 'Breast carcinoma') AND ('Metastasis' OR 'Metastases'), And ('Salivary glands' OR 'Parotid gland' OR 'Submandibular gland' OR 'Sublingual gland'). We also searched all related journals manually. The reference list of all articles was also checked. Our research revealed a total of 48 relevant papers with 55 patients. Parotid was the most predominantly affected salivary gland. 14.5% of patients died with a mean survival time of 7 months. It can be concluded from this research that Breast cancer metastasizing to salivary glands is a rare occurrence. Careful evaluation of these cases is needed in order to raise awareness of these lesions and gain a better understanding of their characteristics.

6.
Front Oncol ; 14: 1420956, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39234395

RESUMO

Background and aim: The prognosis of microsatellite stable (MSS)-colorectal cancer liver metastasis (CRCLM) following failure of multi-line therapy remains dismal. The aim of this study is to evaluate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) plus fruquintinib and tislelizumab (HAIC-F-T treatment) for MSS-CRCLM which failed from multiple-line therapy. Methods: From February 2021 to June 2023, 45 patients with MSS-CRCLM after failure of multiple-line therapy who received HAIC combined with fruquintinib and tislelizumab (HAIC-F-T triple treatment) were enrolled. The combination therapy included HAIC regimens with oxaliplatin and 5-fluorouracil or irinotecan, oxaliplatin, and 5-fluorouracil on days 1-2, intravenous tislelizumab (200 mg) before HAIC on day 1, and oral fruquintinb (3 mg/d) on day 3-21, every 4 weeks. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Results: The follow-up ended on June 22, 2024, with a median follow-up time of 17.5 months. The objective response rate was 42.2%, and the disease control rate was 82.2%. The median OS was 15.3 months (95% confidence interval [CI]:12.634-17.966), and the median PFS was 7.5 months (95% CI:5.318-9.682). The independent risk factors related to worse OS were previous PD-1 immunotherapy (P = 0.021) and the number of HAIC-F-T triple treatment cycles of ≤ 2 (P = 0.007). The incidence of grade 3 or higher adverse events (AEs) was 20%, with the most frequent grade 3 or higher AEs being abdominal pain (3/45, 6.7%). Conclusion: HAIC combined with fruquintinib and tislelizumab may be an alternative salvage treatment for patients with MSS-CRCLM following failure of multiple-line therapy.

7.
Adv Biomed Res ; 13: 26, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39234435

RESUMO

Background: Papillary thyroid carcinoma (PTC) is also the most common endocrine malignancy. In the present study, we aimed to evaluate the metastasis pattern of upper mediastinal lymph node involvement in patients with PTC. Materials and Methods: This is a descriptive cross-sectional study that was performed in 2020 in Isfahan, Iran, on 73 patients with PTC who were candidates for total thyroidectomy. Demographic data including age and gender were collected. The frequency distribution of upper mediastinal lymph node involvements and their relationships with mass size, gender, and age, location of tumor in the thyroid gland and involvement of lateral lymph nodes in the neck were evaluated. Results: The mean mass size was 17.27 mm. The most involved thyroid lobe in patients with upper mediastinal lymph node involvement was the right lobe (16.5%). In terms of mediastinal lymph node involvement, there were no significant relationships between the two sexes (P = 0.161), primary mass size (P = 0.151), and thyroid mass location (P = 0.739) with mediastinal lymph node involvement. There was a significant relationship between lateral lymph node involvement of the neck (P = 0.007) and age groups (P = 0.042) with involvement of the upper mediastinal lymph nodes. Based on our results, the upper mediastinal lymph node involvement was more frequent among patients under 40 years of age. Conclusion: Upper mediastinal lymph node metastasis in PTC was significantly more frequent in cases with younger ages (lower than 40 years) and involvements of lateral lymph nodes in the neck.

8.
Clin J Gastroenterol ; 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39242478

RESUMO

Renal leiomyosarcoma metastasis to the pancreas is exceptionally rare. Here, we present a case of metastatic recurrence in the pancreas seven years after renal leiomyosarcoma resection. A 73-year-old female with a history of renal leiomyosarcoma surgery seven years prior presented with a well-defined 40 × 30 mm pancreatic tail tumor detected by a computed tomography (CT) scan. The tumor exhibited hypo-enhancement in the arterial phase and a progressive enhancement pattern toward the equilibrium phase, similar to pancreatic cancer. Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) revealed bundles of spindle cells that matched those in the previously resected renal sample. Immunohistochemistry showed positive staining for desmin, confirming the diagnosis of pancreatic metastasis from renal leiomyosarcoma. The patient underwent a distal pancreatectomy to remove the metastatic lesion. The extended interval of seven years before the detection of metastasis underscores the challenges in monitoring and diagnosing metastatic patterns of renal leiomyosarcoma. EUS-FNB can assist in distinguishing metastatic pancreatic leiomyosarcoma from primary pancreatic cancer, thus influencing treatment decisions.

9.
Turk J Med Sci ; 54(4): 804-810, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39295619

RESUMO

Background/aim: Uterine leiomyosarcomas (uLMS) are extremely rare high-grade tumors with a poor prognosis. Their etiopathogenesis remains largely unknown. The uterus is the most frequent site for LMS. uLMS and uterine leiomyoma (uLM) must frequently be differentiated in patients with a uterine mass. Nicotinamide N-methyltransferase (NNMT), a cytoplasmic protein, is involved in the progression and spread of a variety of cancer types. The expression of NNMT in a mesenchymal malignancy was not examined previously. This study represents the first investigation into NNMT expression in uLMS, uLM and benign uterine myometrium and correlates NNMT overexpression with worse prognosis in uLMS. Materials and methods: The expression of NNMT was investigated by immunohistochemistry on formalin-fixed paraffin-embedded tissue of uLMS in 31 patients, uLM in seven patients and benign myometrial in 31 patients. Results: The expression of NNMT in uLMS was markedly higher than in uLM and normal myometrial tissue (p < 0.001). The expression of NNMT in early stage uLMS was lower than in advanced stage disease (p = 0.034). NNMT expression was an independent prognostic factor in predicting recurrence-free survival in uLMS (p = 0.037). Conclusion: NNMT can aid in the preoperative differentiation of uLMS and uLM. The consequences of NNMT overexpression, such as the activation and inactivation of oncoproteins and tumor suppressor proteins, respectively, as well as the enrichment of the cancer stem cell population, overlap with the major mechanisms responsible for poor prognosis in mesenchymal tumors. NNMT may be investigated further in the context of antitumor treatment in patients with mesenchymal malignancies.


Assuntos
Leiomiossarcoma , Nicotinamida N-Metiltransferase , Neoplasias Uterinas , Humanos , Feminino , Leiomiossarcoma/metabolismo , Leiomiossarcoma/mortalidade , Leiomiossarcoma/patologia , Neoplasias Uterinas/metabolismo , Neoplasias Uterinas/mortalidade , Neoplasias Uterinas/genética , Neoplasias Uterinas/patologia , Pessoa de Meia-Idade , Prognóstico , Adulto , Nicotinamida N-Metiltransferase/metabolismo , Nicotinamida N-Metiltransferase/genética , Biomarcadores Tumorais/metabolismo , Idoso , Leiomioma/metabolismo , Leiomioma/patologia , Leiomioma/genética , Imuno-Histoquímica
10.
JTCVS Open ; 20: 174-182, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39296460

RESUMO

Objective: In patients with non-small cell lung cancer, lymph node assessment is essential for appropriate staging. The intrapulmonary lymph nodes (IPLNs) should be considered when assigning the N stage but are infrequently evaluated in Colombian centers, resulting in understaging that may hinder optimal treatment. Methods: We conducted a prospective study of IPLN dissection in patients with clinical stage I or II non-small cell lung cancer who underwent surgical resection at 9 institutions in Colombia between 2021 and 2023. IPLN dissection was performed by trained surgeons who collected lymph nodes from fresh specimens after resection and before formalin fixation. Results: One hundred patients were eligible for the analysis. Their mean age was 67 ± 10.9 years, and 76% were women. Most (74%) had adenocarcinoma, 20% had neuroendocrine tumors, and 6% had squamous cell carcinoma. Successful sampling and histopathologic analysis of at least one IPLN station was obtained in 85% of patients, 9% had upstaging due to positive N2 lymph nodes, and 5% had upstaging due to positive N1 lymph nodes. Among the patients with pN0 or pN1 disease, 3.2% (3 out of 91) were upstaged exclusively due to positive IPLNs. Conclusions: Fresh-specimen dissection to collect IPLNs is appropriate and feasible to achieve more accurate pathological staging in Colombian lung cancer patients. In clinical N0 patients, IPLN dissection maximizes selection for adjuvant therapy.

11.
Int Immunopharmacol ; 142(Pt B): 113195, 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39303544

RESUMO

Host microbes are increasingly recognized as key components in various types of cancer, although their exact impact remains unclear. This study investigated the functional significance of Staphylococcus aureus (S. aureus) in breast cancer tumorigenesis and progression. We found that S. aureus invasion resulted in a compromised DNA damage response process, as evidenced by the absence of G1-phase arrest and apoptosis in breast cells in the background of double strand breaks production and the activation of the ataxia-telangiectasia mutated (ATM)-p53 signaling pathway. The high-throughput mRNA sequencing, bioinformatics analysis and pharmacological studies revealed that S. aureus facilitates breast cell metastasis through the innate immune pathway, particularly in cancer cells. During metastasis, S. aureus initially induced the expression of RIG-I-like receptors (RIG-I in normal breast cells, RIG-I and MDA5 in breast cancer cells), which in turn activated NF-κB p65 expression. We further showed that NF-κB p65 activated the CCL5-CCR5 pathway, contributing to breast cell metastasis. Our study provides novel evidence that the innate immune system, triggered by bacterial infection, plays a role in bacterial-driven cancer metastasis.

12.
World J Exp Med ; 14(3): 93869, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39312697

RESUMO

BACKGROUND: Anaplastic thyroid cancer (ATC) is an aggressive, rare malignancy associated with rapid growth and metastasis, and a very poor prognosis. We investigated the clinical characteristics, survival outcomes and independent prognostic factors associated with anaplastic thyroid cancer. AIM: To assess to what extent the interaction between age and tumor stage affects mortality. METHODS: A total of 622 patients diagnosed with anaplastic thyroid cancer, between 2010 and 2017 were enrolled in our study by retrieving data from the Surveillance, Epidemiology and End Results (SEER) database. We analyzed demographics, clinical characteristics, overall mortality (OM) and cancer specific mortality (CSM) of ATC. Variables with a P value < 0.1 were incorporated into the multivariate cox model to determine the independent prognostic factors. Furthermore, we analyzed the interaction between age and tumor stage on mortality. RESULTS: In the multivariate analyses, the divorced/separated population had a lower OM [hazard ratio (HR) = 0.63, 95%CI: 0.42-0.94, P < 0.05] and CSM (HR = 0.61, 95%CI: 0.40-0.92, P < 0.05). OM was higher in tumors with direct extension only (HR = 6.26, 95%CI: 1.29-30.42, P < 0.05) and tumors with distant spread (HR = 5.73, 95%CI: 1.34-24.51, P < 0.05). CSM was also higher in tumors with direct extension (HR = 5.05, 95%CI: 1.05-24.19, P < 0.05) and tumors with distant spread (HR = 4.57, 95%CI: 1.08-19.29, P < 0.05). Mortality was not adversely affected by lymph node involvement. OM was lower in patients who received radiation (HR = 0.66, 95%CI: 0.53-0.83, P < 0.01), chemotherapy (HR = 0.63, 95%CI: 0.50-0.79, P < 0.01) or surgery (HR = 0.53, 95%CI: 0.43-0.66, P < 0.01). CSM was also lower in patient who received radiation (HR = 0.64, 95%CI: 0.51-0.81, P < 0.01), chemotherapy (HR = 0.62, 95%CI: 0.50-0.78, P < 0.01) or surgery (HR = 0.51, 95%CI: 0.41-0.63, P < 0.01). There was no significant interaction between age and tumor stage that affected mortality. CONCLUSION: In this large US SEER database retrospective study, we found the mortality to be higher in advanced stage tumors with direct extension and distant metastasis. However, patients who received aggressive therapy showed a better overall survival. The aim of our study is to emphasize the importance of detecting ATC at an early stage and provide aggressive therapy to these patients. Since advanced stage ATC is associated with a dismal prognosis, we emphasize the need for randomized control trials and development of novel therapies that will be used to treat ATC.

13.
Rozhl Chir ; 103(8): 313-317, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39313360

RESUMO

The authors present the case of a 71-year-old female patient who was operated on for 16 days of abdominal pain. The work points to malignant melanoma as a rare cause of abdominal pain and then shows the inscrutability of malignant melanoma and the importance of a multidisciplinary approach to this type of disease including subsequent dispensary by an oncologist. The emphasis on the prevention of this disease is an integral part of this approach.


Assuntos
Dor Abdominal , Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/secundário , Melanoma/complicações , Feminino , Idoso , Dor Abdominal/etiologia , Neoplasias Cutâneas/secundário , Neoplasias Cutâneas/patologia
14.
SAGE Open Med Case Rep ; 12: 2050313X241275339, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39314217

RESUMO

Pleomorphic adenoma is a benign tumor and the most common salivary gland neoplasm. Metastasizing pleomorphic adenoma shares histological characteristics with pleomorphic adenoma but exhibits malignant behavior, including local lymph node involvement and/or distant metastasis. Several potential risk factors for metastasizing pleomorphic adenoma have been identified, some of which are associated with incomplete tumor clearance due to inadequate surgical techniques used in the treatment of primary pleomorphic adenoma. Here, we present a rare case of metastasizing pleomorphic adenoma originating from the parotid gland and describe its clinical features. The patient was a 75-year-old female with a surgical history of enucleation of a pleomorphic adenoma in the left parotid gland. Total parotidectomy and left neck dissection were performed for the left parotid tumor this time, and the patient attended one postoperative outpatient visit but subsequently was lost to follow-up.

15.
Front Med (Lausanne) ; 11: 1436774, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39314226

RESUMO

Clonal MAPK-pathway activating mutations in the MAP2K1 (MEK1) gene are present in approximately 9% of cutaneous melanomas. These mutations are divided into three classes: RAF-dependent, RAF-regulated, RAF-independent. Cell lines with class-2 or RAF-regulated MAP2K1-mutations are most responsive to MEK-inhibitors. We present a patient with a class-2 MAP2K1-mutant stage IV-M1d melanoma who experienced extra- and intracranial progressive disease following treatment with immune-checkpoint inhibitors. The patient was treated with the MEK-inhibitor trametinib (2 mg OD) to which a low-dose of dabrafenib (50 mg BID) was added to mitigate skin-toxicity. Following documentation of a partial response (PR), she developed one new, and increase in volume of two pre-existing brain metastases that were treated with stereotactic radiosurgery (SRS) while continuing trametinib and dabrafenib. Thereafter, a deep partial radiologic and metabolic response both extra-and intra-cranially was achieved and is ongoing 88 weeks after initiating trametinib. She experienced no grade > 2 adverse events. Focal post-radiation necrosis at site of an irradiated brain metastasis developed 9 months after SRS and is successfully being treated with low-dose bevacizumab. This is the first published case of a durable intracranial disease control with the MEK-inhibitor trametinib of a stage IV-M1d class-2 MAP2K1-mutant melanoma. This illustrates the utility of NGS profiles that include class-1/2 MAP2K1-mutations in patients with melanoma and other malignancies to provide valuable information on a potentially active individualized treatment option. A prospective clinical trial that further evaluates the efficacy of MEK-inhibitor therapies in MAP2K1-mutated tumors is justified.

16.
Front Med (Lausanne) ; 11: 1391621, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39314227

RESUMO

Background: The status of the sentinel lymph nodes (SLNs) is an important prognostic factor for many different types of cancer. The one-step nucleic acid amplification (OSNA) assay has emerged as a rapid intraoperative molecular diagnostic tool for LN metastasis detection. We aimed to evaluate and summarize the value of the OSNA assay for the diagnosis of SLN metastasis in cytokeratin 19 (CK19)-positive breast cancer. Methods: To evaluate the diagnostic value, the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were pooled. The threshold effect, followed by subgroup analysis, was performed to explore the source of heterogeneity. A sensitivity analysis was performed to assess the stability of this meta-analysis model. Fagan plots and likelihood ratio scattergrams were used to explore the potential clinical significance. Results: A total of 29 eligible studies, which consisted of 5,331 patients with 10,343 SLNs, were included in this meta-analysis. The pooled sensitivity, specificity, PLR, NLR, and DOR were 0.86 (95% CI: 0.85-0.88), 0.94 (95% CI, 0.94-0.95), 18.00 (95% CI, 13.54-23.92), 0.13 (95% CI, 0.10-0.17), and 138.99 (95% CI, 86.66-222.92), respectively. The AUC was 0.97 (95% CI, 0.95-0.98). Sensitivity analysis showed that four studies had an impact on the pooled results and mainly contributed to the heterogeneity. Fagan's nomogram revealed that the prior probability was 50%, the post-probability positive was 95%, and the post-probability negative was 11%. Discussion: Our results suggested that OSNA can predict the occurrence of SLN metastasis in CK19-positive breast cancer. However, more well-designed and multicenter diagnostic tests are needed to validate our results.

17.
Radiol Case Rep ; 19(12): 5877-5881, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39314664

RESUMO

Choriocarcinoma is a type of gestational trophoblastic disease that occurs as a complication of pregnancy-related events. The gestational trophoblastic disease includes both benign and malignant conditions including complete and partial mole, invasive mole, choriocarcinoma, and placental site trophoblastic disease. Choriocarcinoma generally presents with pervaginal bleeding, symptoms of anemia, and symptoms of its metastatic lesion. The common sites of metastasis are the lung, vagina, brain, and liver. The gastrointestinal (GI) tract is an uncommon site of metastasis occurring in <5% of patients. Upper GI bleeding as presenting complaints without pervaginal bleeding is also very rare with only a few reported cases. Here we present a case of 29 years young female who presented in our emergency department with complaints of hematemesis and altered sensorium where clinical suspicion was peptic ulcer disease but imaging modality with computed tomography showed hypervascular lesions in the brain with suspicion of choriocarcinoma. With further imaging and laboratory tests, confirmatory diagnosis of choriocarcinoma was made. This case highlights the importance of imaging in the diagnosis of choriocarcinoma where the history of the patient is misleading.

18.
Pan Afr Med J ; 48: 56, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39315063

RESUMO

Liposarcoma is a rare primitive mesenchymal tumor, developed at the expense of adipose tissue and with a preferential location in the thigh. We report an observation of liposarcoma in the buttock. A 56-year-old man, presented with a tumor of the right buttock for 2 years. Examination revealed an inflammatory, ulcerated tumor in the upper-external quadrant of the right buttock, measuring about 8 cm. Bilateral inguinal adenopathies were associated. The diagnostic hypotheses were: a squamous cell carcinoma, a cutaneous lymphoma, and cutaneous metastases. An anatomical examination confirmed the diagnosis of myxoid round-cell liposarcoma. The extension work-up appeared compatible with secondary pleuropulmonary, hepatic, cutaneous, and lymph node neoplastic localizations. The patient was treated with chemotherapy with the Adriamycin-carboplatin protocol. The evolution was rapidly fatal after a few weeks after the first course of chemotherapy. It should be evoked in front of any ulcerated tumor of the buttock.


Assuntos
Lipossarcoma Mixoide , Neoplasias Cutâneas , Humanos , Nádegas/patologia , Pessoa de Meia-Idade , Masculino , Lipossarcoma Mixoide/patologia , Lipossarcoma Mixoide/diagnóstico , Lipossarcoma Mixoide/tratamento farmacológico , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/diagnóstico , Evolução Fatal , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Doxorrubicina/administração & dosagem
20.
Heliyon ; 10(18): e37346, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39315148

RESUMO

Objectives: About 90 % of all colorectal cancer (CRC) fatalities are caused by the metastatic spread of primary tumors, which is closely correlated with patient survival and spreads by circulating tumor cells (CTCs). The epithelial-mesenchymal transition (EMT) that characterizes CTCs is associated with a poor prognosis. Organotropic metastasis is dictated by the transmission of miRNAs by cancer-derived exosomes. The purpose of this research is to examine PKS + E's function. Coli in CRC metastases and exosomal miR-885-5p suppression. Methods: A cohort of 100 patients (50 CRC, 50 healthy) underwent colonoscopy screenings from February 2018 to August 2021. Exosomes were isolated using ultracentrifugation, and exosomal miRNA was analyzed using sequencing and qPCR. Results: Among the patients, 40 tested positive for E. coli (12 CRC, 23 healthy). Serotyping revealed that 68.57 % harbored the PKS gene. Exosomal miR-885-5p levels were significantly altered in CRC patients with PKS + E. coli. Intriguingly, our findings indicate that exosomes derived from EMT-CRC cells did not affect miR-885-5p synthesis in HUVECs. Moreover, we observed that the levels of miR-885-5p in both exosomes and the total CRC-conditioned medium were comparable upon isolation of exosomes from CRC cells. What's more, an increased expression of miR-558-5p within the tumors, and the group that received exosome treatment, as well as the EMT-HCT116 group, exhibited a higher occurrence of distant metastasis. Conclusion: PKS + E. By inhibiting exosomal miR-885-5p, coli is linked to CRC metastases, offering a possible target for therapeutic intervention.

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