Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 28
Filtrar
Mais filtros

Base de dados
Tipo de documento
País de afiliação
Intervalo de ano de publicação
1.
Apoptosis ; 25(3-4): 233-246, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31974865

RESUMO

Platinum based drugs alone or in combination with 5FU and docetaxel are common regimen chemotherapeutics for the treatment of advanced OSCC. Chemoresistance is one of the major factors of treatment failure in OSCC. Human RNA helicase DDX3 plays an important role in cell proliferation, invasion, and metastasis in several neoplasms. The potential role of DDX3 in chemoresistance is yet to be explored. Enhanced cancer stem cells (CSCs) population significantly contributes to chemoresistance and recurrence. A recent study showed that m6A RNA regulates self-renewal and tumorigenesis property in cancer. In this study we found genetic (shRNA) or pharmacological (ketorolac salt) inhibition of DDX3 reduced CSC population by suppressing the expression of FOXM1 and NANOG. We also found that m6A demethylase ALKBH5 is directly regulated by DDX3 which leads to decreased m6A methylation in FOXM1 and NANOG nascent transcript that contribute to chemoresistance. Here, we found DDX3 expression was upregulated in both cisplatin-resistant OSCC lines and chemoresistant tumors when compared with their respective sensitive counterparts. In a patient-derived cell xenograft model of chemoresistant OSCC, ketorolac salt restores cisplatin-mediated cell death and facilitates a significant reduction of tumor burdens. Our work uncovers a critical function of DDX3 and provides a new role in m6 demethylation of RNA. A combination regimen of ketorolac salt with cisplatin deserves further clinical investigation in advanced OSCC.


Assuntos
Homólogo AlkB 5 da RNA Desmetilase/metabolismo , Cisplatino/farmacologia , RNA Helicases DEAD-box/metabolismo , Resistencia a Medicamentos Antineoplásicos , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cisplatino/uso terapêutico , RNA Helicases DEAD-box/antagonistas & inibidores , RNA Helicases DEAD-box/genética , Desmetilação , Proteína Forkhead Box M1/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Cetorolaco de Trometamina/farmacologia , Cetorolaco de Trometamina/uso terapêutico , Camundongos , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/metabolismo , Proteína Homeobox Nanog/genética , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , RNA Mensageiro/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
2.
Carcinogenesis ; 40(1): 173-183, 2019 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-30395230

RESUMO

Cisplatin alone or in combination with 5FU (5-fluorouracil) and docetaxel (TPF) are common regimen chemotherapeutics for treatment of advanced oral squamous cell carcinoma (OSCC). Despite the initial positive response, several patients experience relapse due to chemoresistance. The potential role of Bcl-2 antiapoptotic members in acquired chemoresistance is yet to be explored. To address this, we designed two different relevant OSCC chemoresistant models: (i) acquired chemoresistant cells, where OSCC lines were treated with conventional chemotherapy for a prolonged period to develop chemoresistance, and (ii) chemoresistant patient-derived cells, where primary cells were established from tumor of neoadjuvant-treated OSCC patients who do not respond to TPF. Among all Bcl-2 antiapoptotic members, Mcl-1 expression (but not Bcl-2 or Bcl-xL) was found to be upregulated in both chemoresistant OSCC lines and chemoresistant tumors when compared with their respective sensitive counterparts. Irrespective of all three chemotherapy drugs, Mcl-1 expression was elevated in OSCC cells that are resistant to either cisplatin or 5FU or docetaxel. In chemoresistant OSCC, Mcl-1 mRNA was upregulated by signal transducer and activator of transcription 3 (STAT3) activation, and the protein was stabilized by AKT-mediated glycogen synthase kinase 3 beta (GSK3ß) inactivation. Genetic (siRNA) or pharmacological (Triptolide, a transcriptional repressor of Mcl-1) inhibition of Mcl-1 induces drug-mediated cell death in chemoresistant OSCC. In patient-derived xenograft model of advanced stage and chemoresistant OSCC tumor, Triptolide restores cisplatin-mediated cell death and facilitates significant reduction of tumor burdens. Overall, our data suggest Mcl-1 dependency of chemoresistant OSCC. A combination regimen of Mcl-1 inhibitor with conventional chemotherapy deserves further clinical investigation in advanced OSCC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Glicogênio Sintase Quinase 3 beta/fisiologia , Neoplasias Bucais/tratamento farmacológico , Proteína de Sequência 1 de Leucemia de Células Mieloides/fisiologia , Fator de Transcrição STAT3/fisiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Diterpenos/farmacologia , Resistencia a Medicamentos Antineoplásicos , Compostos de Epóxi/farmacologia , Fluoruracila/uso terapêutico , Humanos , Masculino , Camundongos , Proteína de Sequência 1 de Leucemia de Células Mieloides/antagonistas & inibidores , Fenantrenos/farmacologia , Proteínas Proto-Oncogênicas c-akt/fisiologia , Taxoides/uso terapêutico
4.
Cureus ; 16(1): e52172, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38344632

RESUMO

Introduction CDK4/6 inhibitors currently approved for patients with hormone-receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer include palbociclib, ribociclib, and abemaciclib. This study aims to report on the treatment outcomes and real-world data regarding the use of CDK4/6 inhibitors in the treatment of ER+/HER2- metastatic breast cancer at a tertiary care institute in Eastern India. Materials and methods The present study is a retrospective analysis of data from patients with metastatic HR+/HER2- breast cancer who were treated with CDK4/6 inhibitors at a tertiary care institute in Eastern India between 2015 and 2022. The data were collected from online records in the departmental files and analyzed for the primary baseline characteristics of the patients, tumors, and response rates, including partial response (PR), complete response (CR), progressive disease (PD), and stable disease (SD), as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1. The treatment administered, progression-free survival (PFS), and toxicity were also evaluated. Results From 2015 to 2022, 24 eligible patients were treated with CDK4/6 inhibitors for metastatic HR+/HER2- breast cancer. The average duration of follow-up was 25 months. Out of the 24 patients, 15 (62.5%) were taking Tab. ribociclib, six (25%) were taking Tab. palbociclib, and three (12.5%) were taking Tab. abemaciclib. CDK4/6 was used as a first-line therapy for 16 patients, while eight patients received it as a second-line treatment. Out of the total number of patients, six (25%) had stable disease, 13 (54.2%) had a partial response, and four (16.7%) had progressive disease. In total, of the eligible patients, five (20.8%) had grade I neutropenia, seven (29.2%) had grade II neutropenia, and four (16.7%) had grade III neutropenia. At five years, the PFS rate estimated by the Kaplan-Meier method was 50% (95% CI: 47.89-69.31). Conclusion Ribociclib and palbociclib have improved PFS in patients with metastatic HR+/HER2- breast cancer. Both drugs have well-tolerated toxicity, allowing patients to continue taking them for an extended period of time. CDK4/6 inhibitors have a higher response rate than the other agents.

5.
J Gastrointest Cancer ; 55(2): 940-949, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38530597

RESUMO

INTRODUCTION/BACKGROUND: Colorectal carcinoma (CRC) is a common malignancy, with its diverse clinical, pathological, and molecular features. The immune microenvironment of a tumor comprises of interplay between various cells and molecules, and has a significant role in deciding the tumor behavior and overall prognosis. PD-L1 (programmed cell death ligand-1) has been implicated in the regulation of the tumor immune microenvironment (TIME). There is limited data regarding the correlation of PD-L1 expression with immune cell profile in CRCs, especially in the Indian setting. The study aimed to assess the PD-L1 expression in CRC tumor cells and its association with TIME, mismatch repair (MMR), and various other clinicopathological parameters. METHODS: This is a hospital-based, cross-sectional observational study. PD-L1 expression was assessed at the protein level by immunohistochemistry and mRNA level by qRT-PCR. Immune cell markers (CD4, CD8, CD20, FOXP3, and CD163) were interpreted using the ImageJ Fiji platform. RESULTS: Of the 104 cases, 21% were PD-L1 positive and were more common in right-sided CRCs. PD-L1 positive cases showed significantly higher concentrations of all T-cell subsets (CD4+ , CD8+ , and FOXP3+), CD20+ B-cells, and CD163+ macrophages were noted. No statistical significance was seen between PD-L1 expression with clinical profile, pathological subtype, grade or stage, mismatch repair status (proficient vs deficient), and survival. CONCLUSIONS: The present study showed a relatively lower frequency of PD-L1 in CRC from the Eastern Indian cohort. The immune cell concentration in the present study was calculated using image analysis-based objectivised methods. Significant correlation of PD-L1 expression in tumor cells with the tumor-infiltrating immune cells indicated its crucial role in the pathobiology of CRC especially by regulating the TIME. Considering the therapeutic implication of PD-L1 in various malignancies, it may be one of the crucial therapeutic targets in a proportion of cases.


Assuntos
Antígeno B7-H1 , Neoplasias Colorretais , Microambiente Tumoral , Humanos , Microambiente Tumoral/imunologia , Antígeno B7-H1/metabolismo , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Transversais , Idoso , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Prognóstico , Adulto , Linfócitos do Interstício Tumoral/imunologia
6.
J Egypt Natl Canc Inst ; 36(1): 11, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38584227

RESUMO

BACKGROUND: The moderate deep inspiratory breath hold (mDIBH) is a modality famed for cardiac sparing. Prospective studies based on this are few from the eastern part of the world and India. We intend to compare the dosimetry between mDIBH and free-breathing (FB) plans. METHODS: Thirty-two locally advanced left breast cancer patients were taken up for the study. All patients received a dose of 50 Gy in 25 fractions to the chest wall/intact breast, followed by a 10-Gy boost to the lumpectomy cavity in the case of breast conservation surgery. All the patients were treated in mDIBH using active breath coordinator (ABC). The data from the two dose volume histograms were compared regarding plan quality and the doses received by the organs at risk. Paired t-test was used for data analysis. RESULTS: The dose received by the heart in terms of V5, V10, and V30 (4.55% vs 8.39%) and mean dose (4.73 Gy vs 6.74 Gy) were statistically significant in the ABC group than that in the FB group (all p-values < 0.001). Also, the dose received by the LADA in terms of V30 (19.32% vs 24.87%) and mean dose (32.99 Gy vs 46.65 Gy) were significantly less in the ABC group. The mean treatment time for the ABC group was 20 min, while that for the free-breathing group was 10 min. CONCLUSIONS: Incorporating ABC-mDIBH for left-sided breast cancer radiotherapy significantly reduces the doses received by the heart, LADA, and left and right lung, with no compromise in plan quality but with an increase in treatment time.


Assuntos
Neoplasias da Mama , Neoplasias Unilaterais da Mama , Humanos , Feminino , Suspensão da Respiração , Neoplasias Unilaterais da Mama/radioterapia , Neoplasias da Mama/radioterapia , Estudos Prospectivos , Coração , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Órgãos em Risco
7.
Oral Oncol ; 142: 106421, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37216834

RESUMO

Intracranial cavernous sinus metastases of oral squamous cell carcinoma (OSCC) are rare, with a reported incidence of 0.4 %. Due to their extremely infrequent presentation the etiology and management modalities of such complications are not clearly represented in the literature. Here we present a case of a 58-year-old male diagnosed with OSCC of Right Lower Alveolus with underlying bone invasion, cT4aN1M0, Stage IV. He underwent Right Hemi-mandibulectomy with Modified Neck Dissection, Pectoralis Major Myocutaneous Flap, and 60 Gy/30# adjuvant radiotherapy. Six months later, the patient was diagnosed with recurrence involving the right infratemporal fossa with associated right cavernous sinus thrombosis. Immunohistochemistry block review showed PDL1 - Positive. The patient was subjected to Cisplatin and Pembrolizumab immunotherapy. After receiving 35 cycles of Pembrolizumab over a period of 2 years the patient is doing well with no recurrence.


Assuntos
Carcinoma de Células Escamosas , Trombose do Corpo Cavernoso , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Masculino , Humanos , Pessoa de Meia-Idade , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/secundário , Neoplasias Bucais/terapia
8.
Cureus ; 15(2): e35083, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36938266

RESUMO

Cervical cancer usually metastasizes to the lung, liver, bone, and brain. Metastasis to the skin from cervical cancer is relatively uncommon. The management options are systemic therapy, palliative radiotherapy, or best supportive care. Here, we report the case of a female patient with cervical cancer, stage IIB, who received radical treatment with radiotherapy and chemotherapy and later presented with disseminated skin nodules. She was treated with combination chemotherapy (nano-dispersible paclitaxel and carboplatin), bevacizumab, and a bone-stabilizing agent (zoledronic acid). There was a complete metabolic response to the therapy. There was also a dramatic improvement in the general condition of the patient. Skin metastasis in cervical cancer often presents as non-tender skin nodules. A biopsy is mandatory to establish the diagnosis. There are no specific guidelines about management. The intention of management is palliative. The combination of chemotherapy and bevacizumab produces substantial clinical improvement.

9.
Cureus ; 15(5): e39229, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37337489

RESUMO

Renal cell carcinoma (RCC) commonly metastasizes to various organs such as the lungs, liver, bones, and brain. However, isolated metastases to the head and neck region, especially the larynx, are very rare. This report presents a case of laryngeal growth that was eventually confirmed to be a metastatic deposit from an undiagnosed RCC. We report a case of a 66-year-old male who presented to the clinic with painless neck swelling and a change in voice. The scan showed a soft tissue mass in the thyroid cartilage. Histopathology of the resected laryngeal tumor confirmed metastatic clear cell carcinoma. A metastatic workup revealed a renal mass, and the patient underwent laparoscopic adrenal-sparing left cytoreductive nephrectomy. The histopathological examination established the diagnosis of clear cell RCC. Subsequently, the patient was treated with pembrolizumab and lenvatinib. Follow-up imaging showed no residual or recurrent lesions. This case highlights the rarity of laryngeal metastasis from RCC and the importance of an accurate diagnosis through advanced imaging and histopathological examination.

10.
J Gastrointest Cancer ; 54(2): 606-613, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35749055

RESUMO

BACKGROUND: The incidence of perineural invasion (PNI) in patients with gastric cancer (GC) is high, and patients with PNI positive disease have a poor prognosis compared to PNI-negative disease. The present study aims to study the incidence and evaluate the impact of PNI on the survival outcome of a cohort of South Asian GC patients. MATERIAL AND METHODS: All consecutive patients undergoing curative gastrectomy were included in the study. The incidence of PNI and correlation with different clinico-pathological features and overall survival was performed. RESULTS: A total of 59.54% had PNI-positive disease and the median OS of PNI + ve patients was 29.3 months, while it was not reached in PNI-ve patients. The PNI positivity was a significant prognostic factor for overall survival both on univariate and multivariate analysis. On TNM-PNI staging, those with TNM stage I/II patients with PNI + ve disease had similar OS to all stage III patients (p = 0.835) and were worse than that of PNI-ve patients (p < 0.05). CONCLUSION: The incidence of PNI in gastric cancer is high. The inclusion of PNI with AJCC-TNM staging may better stratify prognostic staging in curatively treated gastric cancer patients.


Assuntos
Neoplasias Gástricas , Humanos , Estadiamento de Neoplasias , Neoplasias Gástricas/patologia , Estudos Retrospectivos , Nervos Periféricos/patologia , Invasividade Neoplásica/patologia , Prognóstico , Gastrectomia , Taxa de Sobrevida
11.
BMJ Case Rep ; 15(6)2022 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-35732362

RESUMO

Metastasis to inguinal lymph nodes from breast cancer is extremely rare and only a handful of cases have been reported in the literature to date. We report a case of a postmenopausal female patient who was a treated case of right breast cancer and developed inguinal metastases after 9 months. An excisional biopsy of the lesion confirmed the diagnosis. A positron emission tomography-CT scan revealed retropectoral and pelvic lymphadenopathy. The patient was treated with palliative radiotherapy to the inguinal and pelvic regions followed by palliative chemotherapy. The patient survived for 4 months after the detection of inguinal metastasis.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Feminino , Virilha/patologia , Humanos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Metástase Linfática/patologia , Tomografia por Emissão de Pósitrons
12.
BMJ Case Rep ; 15(7)2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-35835487

RESUMO

Primary gastric melanoma is a rare clinical finding. It presents with upper gastrointestinal symptoms like abdominal pain, weight loss and melaena. It is often difficult to differentiate a primary gastric melanoma from primary cutaneous melanoma with gastric metastasis. Upper gastrointestinal endoscopy and biopsy of the lesion for histopathology and immunohistochemistry help to reach a definite diagnosis. We report a case of primary gastric melanoma with metastases to the liver and bone. The patient was treated with palliative radiotherapy, palliative chemotherapy and a bone-stabilising agent.


Assuntos
Melanoma , Segunda Neoplasia Primária , Neoplasias Cutâneas , Neoplasias Gástricas , Biópsia , Humanos , Melanoma/diagnóstico , Melanoma/patologia , Melanoma/terapia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia
13.
J Egypt Natl Canc Inst ; 34(1): 28, 2022 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-35781139

RESUMO

INTRODUCTION: COVID-19 patients with cancer had poorer outcomes due to immunosuppression during cancer care, poor general condition, and other comorbidities. The study was conducted to present the real-world analysis of the effect of treatment interruptions on the outcomes of patients treated with radiation therapy during the first wave of the COVID-19 pandemic in a tertiary care institute in India. MATERIALS AND METHODS: The study is a retrospective observational cohort study on cancer patients undergoing radiation therapy from March 2020 to January 2021. The study's primary outcome was to analyze the effect of treatment interruptions on the outcomes of patients treated with radiation therapy during the first wave of COVID-19 pandemic. RESULTS: Between March 2020 to January 2021, 218 eligible patients undergoing radiation therapy were found for the study. Among the 218 patients, 25 patients (11.47%) were found positive for COVID-19, while 193 patients (88.53%) were negative for COVID-19. Among COVID-19-positive patients, ten patients had < 3 weeks of treatment interruption, while 15 patients had > 3 weeks of treatment interruptions. After recovering from COVID-19, treatment was resumed and completed for 15 (60.00%) of the COVID-19-positive patients. In comparison, 13 patients (52.00%) were lost to follow-up. Three of the COVID-19-positive patients died. The disease was clinically controlled in 12 (48.00%) of the COVID-19-positive patients, and the patients reported locoregional disease progression in 10 (40.00%). Among the 193 COVID-19-negative patients, 32 patients (16.58%) had treatment interruption. Twelve patients (37.50%) had treatment interruptions for less than 1 week. There was a significant difference in the delay of radiation treatment delivery by 2 weeks (11 fractions) in COVID-19-positive patients compared to only two fractions delay in COVID-19-negative patients. CONCLUSION: COVID-19 impacted the treatment outcomes in both COVID-19-positive and COVID-19-negative cohorts of patients. There was a longer duration of treatment interruptions in the COVID-19-positive patients, leading to fewer patients completing the radiation treatment and thereby increased locoregional disease progression. There was a significant difference in the delay in treatment between the two groups.


Assuntos
COVID-19 , Neoplasias , COVID-19/epidemiologia , Progressão da Doença , Humanos , Neoplasias/epidemiologia , Neoplasias/radioterapia , Pandemias , Estudos Retrospectivos , Atenção Terciária à Saúde
14.
Cureus ; 14(3): e23568, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35494897

RESUMO

Introduction Post-mastectomy radiation in left-sided breast cancer in women continues to pose a significant risk to the underlying lungs and heart. This study analyzed the difference in planning target volume (PTV) coverage and dose to the organs at risk (OAR) by using three different planning methods for the same patient - three-dimensional conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), and volumetric-modulated arc therapy (VMAT). Material and methods Thirty-five left-sided breast cancer patients' post-mastectomy were included in this study, and three different plans for adjuvant radiation were created using 3D-CRT, IMRT, and VMAT. The prescribed dose was 50Gy in 25 fractions. Kruskal-Wallis analysis of variance (ANOVA) was done, followed by a pairwise t-test to establish a hierarchy of plan quality and dosimetric benefits. The plans were compared with PTV95, homogeneity index (HI), conformity index (CI), hotspot (V107%), left lung V20Gy, mean lung dose, heart V25Gy, mean heart dose, and integral dose (ID) to the body. Results Both VMAT and IMRT led to improved PTV95% coverage (95.63±1.82%, p=0.000 in VMAT; 93.70±2.16 %, p=0.000; 81.40±6.27% in 3D-CRT arm) and improved CI (0.91±0.06 in IMRT [p<0.05] and 0.96±0.02 for VMAT plans [p<0.05]) as compared to 3D-CRT (0.66±0.11), which was statistically significant on pairwise analysis. In contrast, the difference in HI and reduction in hotspots were not significantly different. Left lung V20 was statistically very different between the three arms with the highest values in IMRT (36.64±4.45) followed by 3D-CRT (34.80±2.24) and the most negligible value in VMAT (33.03±4.20). Mean lung dose was also statistically different between the three arms. There was a statistically significant difference in mean heart dose between the three arms on pairwise analysis. Both the inverse planning methods led to a statistically significant increase in low dose volume (V5 and V10) of the ipsilateral lung, opposite lung, and heart, and increased ID to the body excluding the PTV. Conclusion While both the inverse planning modalities led to increased coverage, better CI, and better HI and decreased high dose volumes in OARs, there was increased low volume irradiation of heart, lungs, and body with VMAT faring marginally better than IMRT in coverage and decreasing lung irradiation with comparable heart irradiation.

15.
Oncogene ; 41(45): 4929-4940, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36182968

RESUMO

Cisplatin, 5FU and docetaxel (TPF) are the most common chemotherapy regimen used for advanced OSCC. However, many cancer patients experience relapse, continued tumor growth, and spread due to drug resistance, which leads to treatment failure and metastatic disease. Here, using a CRISPR/Cas9 based kinome knockout screening, Misshapen-like kinase 1 (MINK1) is identified as an important mediator of 5FU resistance in OSCC. Analysis of clinical samples demonstrated significantly higher MINK1 expression in the tumor tissues of chemotherapy non-responders as compared to chemotherapy responders. The nude mice and zebrafish xenograft experiments indicate that knocking out MINK1 restores 5FU mediated cell death in chemoresistant OSCC. An antibody based phosphorylation array screen revealed MINK1 as a negative regulator of p53. Mechanistically, MINK1 modulates AKT phosphorylation at Ser473, which enables p-MDM2 (Ser 166) mediated degradation of p53. We also identified lestaurtinib as a potent inhibitor of MINK1 kinase activity. The patient derived TPF resistant cell based xenograft data suggest that lestaurtinib restores 5FU sensitivity and facilitates a significant reduction of tumor burden. Overall, our study suggests that MINK1 is a major driver of 5FU resistance in OSCC. The novel combination of MINK1 inhibitor lestaurtinib and 5FU needs further clinical investigation in advanced OSCC.


Assuntos
Proteínas Proto-Oncogênicas c-akt , Proteína Supressora de Tumor p53 , Camundongos , Animais , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Camundongos Nus , Peixe-Zebra/metabolismo , Recidiva Local de Neoplasia/tratamento farmacológico , Cisplatino/farmacologia , Fluoruracila/uso terapêutico , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteínas Serina-Treonina Quinases/genética
16.
Future Sci OA ; 8(9): FSO821, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36788987

RESUMO

Telemedicine has revolutionized areas of medical practice and care. It has a potential in field of continuum of cancer care in India. SARS-CoV-2 has highlighted the potential use of this tool effectively. Scope of newer applications of telemedicine in field of cancer is reviewed in current paper enlisting benefits to patient, healthcare providers and centers in a developing country like India. Each of them is supported by appropriate evidence and examples. An analysis of strengths and opportunities when compared with weakness and threats brings out how telemedicine can redistribute oncology work force in a rational way and minimize disruption caused by the pandemic. Telemedicine can be utilized in cancer management starting from prevention, screening, diagnosis, treatment and rehabilitation to palliative care.


Specialists working for decades in the field of oncology are the best persons to endorse telemedicine, as they can leverage its use to its full potential. The present article is a rigorous review of past literature on telemedicine as well as proposed uses of technologies based on experiences of the authors. It will strengthen promotive, preventive, curative and rehabilitative healthcare delivery.

17.
Cureus ; 14(10): e30589, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36420233

RESUMO

Introduction Lung cancer is the most common cancer, and it is the leading cause of cancer-related death. Smoking is the most common risk factor for the development of lung cancer. There is a lack of data on the comorbidities and outcomes of advanced non-small cell lung cancer (NSCLC) in the eastern part of India. This prospective study evaluated the impact of comorbidity scores on overall survival (OS) in these patients. Method This prospective cohort study was conducted on newly diagnosed advanced NSCLC patients between June 2020 and April 2021. These patients were given platinum-based doublet chemotherapy guided by histology and targeted therapy based on molecular studies. Comorbidities were assessed using the Charlson Comorbidity Index (CCI), Simplified Comorbidity Score (SCS), and Adult Comorbidity Evaluation-27 (ACE-27). The outcome assessed was OS. Overall survival was calculated in days from the date of start of anticancer therapy to the date of last follow-up or date of death. All enrolled patients were followed at regular intervals whenever they visited the hospital and telephonically until April 2022. The patients who were alive on April 30, 2022, were censored. The survival probability and median OS were calculated by Kaplan-Meier analysis, and group differences in comorbidity scores were analyzed with the log-rank test. A Cox proportional hazard analysis was performed to look for factors affecting overall survival. Results A total of 114 patients were enrolled in the study period, and the mean age of patients was 56.54 ± 11.03 years. Most of the patients were males (68.4%), and 52.6% were smokers. Adenocarcinoma was the most common histology (73.7%), followed by squamous cell carcinoma (25.4%). The median OS was 127 days (95% CI, 60-193 days). 33.4% of the patients had a CCI score of 0, a CCI score of 1 was seen in 57%, and ≥2 scores in 9.6%. SCS scores ≤9 and >9 were seen in 92.1% and 7.9% of patients, respectively. The ACE-27 score was none in 41 subjects, mild in 59, moderate in 12, and 2 NSCLC subjects had severe ACE-27 scores. The median OS for patients with a CCI score of 0 was 275 days (95% CI, 7-543 days), 114 days (95% CI, 85-142 days) for subjects with a CCI score of 1, and 402 days (95% CI, 0-844 days) for patients with a CCI score ≥2 (log-rank p = 0.215). Individuals with an SCS score ≤9 had a median OS of 175 days (95% CI, 91-258 days), and the median OS was 92 days (95% CI, 80-103 days) for patients with an SCS score >9 (log-rank p = 0.302). Median OS of the patients with ACE-27 score 0,1,2,3 were 297 days (95% CI, 76- 517 days), 117 days (95% CI, 81-152 days), 87 days (95% CI, 49-124 days) and 66 days, respectively (log-rank p=0.457). There was no statistical significance between comorbidity scores and OS. Worse OS was independently associated with poor performance status Eastern Cooperative Oncology Group (ECOG) ≥2 (hazard ratio [HR] 3.266; 95% CI 1.785-5.978; p = 0.00), neutrophil-to-lymphocyte ratio (NLR) <3 (HR, 2.35 95% CI 1.18-4.702; p = 0.015) and patients who were given compassionate tyrosine kinase inhibitors (TKIs) (HR, 7.396 95% CI 3.531-15.490; p = 0.000). Conclusions In our study, the advanced NSCLC patients who were given chemotherapy or oral TKIs showed no significant influence of comorbidities on overall survival. Factors independently associated with the worst survival were poor performance status (ECOG ≥ 2), NLR < 3, and patients who were given TKIs on a compassionate basis.

18.
Cureus ; 13(11): e19790, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34956782

RESUMO

Worldwide lung cancer is the most common cause of cancer mortality. Most of the lung cancer patients present with advanced disease at the time of diagnosis, and in that case, the prognosis is poor even with treatment. The most common sites of metastases in non-small-cell lung cancer are the brain, bone, liver, and adrenal gland. Metastasis to the stomach is extremely rare, which carries with itself a more dismal prognosis. Here we are reporting a rare case of adenocarcinoma lung with metastasis to the stomach, which was initially a diagnostic dilemma. The patient survived for 30 months from the diagnosis of gastric metastasis by management predominantly with immunotherapy.

19.
Cureus ; 13(12): e20813, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35141071

RESUMO

Osteosarcoma is the most common skeletal malignancy and commonly metastasis to lung and bone. Here we report a case of osteosarcoma of the right knee with metastasis to the lower and inner quadrant of the breast along with axillary, mediastinal, retroperitoneal and inguinal lymphadenopathy with lung and liver metastasis. The diagnosis of breast metastasis was confirmed by ultrasonography-guided biopsy and immunohistochemistry (IHC). So this report highlights the rarest metastasis to breast and axillary lymph node from an osteosarcoma of the right knee primary.

20.
Cureus ; 13(12): e20298, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35036180

RESUMO

Male breast cancer (MBC) is a rare malignancy with an overall incidence of less than 1%. The epidemiological data of MBC is very limited owing to its rarity, particularly data from India. Hence, it is important to study different aspects of this rare malignancy. This paper reports a single-center experience from India that evaluated the clinicopathological behavior of MBC, their management, and outcomes. This was a retrospective review, which included 18 patients managed between 2013 to 2021. Seventeen out of the 18 patients were aged ≥50 years; the median age was 60 years. Left sides were affected more than right (left: 11, right: seven), and the most commonly affected quadrant was central (n=15/17, 88.2%). The most common (n=14) surgery was modified radical mastectomy (MRM), and the invasive ductal carcinoma was the most common (n=14) histological finding. Most cases were estrogen-receptor (ER) and progesterone-receptor-positive (n=15/18, 83.3%). The present study, though with a small sample size, adds valuable information to the literature about this rare occurrence in men.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA