Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We herein describe a 4-year-old boy who after being treated for pneumonia showed an abnormal shadow at the hilus of the right lung on chest X-rays with continued inflammatory findings in his laboratory data. CT and MR investigations suggested the existence of a neoplasm at that site. An open biopsy was thus performed for a definite diagnosis. The histological findings and the expression of TPM3-ALK fusion gene confirmed a diagnosis of an inflammatory myofibroblastic tumor. A right upper and middle lobectomy including the tumor was thus performed for a complete resection. In addition to the histological diagnosis, the detection of the tumor specific fusion gene provided objective evidence in making a diagnosis.
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PMID:A case of an inflammatory myofibroblastic tumor in the lung which expressed TPM3-ALK gene fusion. 1706 37

Crizotinib (Pfizer, CA, USA) is an oral small-molecule RTK inhibitor that targets ALK and MET, and potentially other RTKs. Crizotinib was approved by the US FDA on 26 August 2011 for the treatment of ALK-rearranged non-small-cell lung cancer (NSCLC), as detected by ALK break-apart FISH assay. This conditional approval was based on response rates of 50-61% from 255 ALK-rearranged NSCLC patients enrolled in two ongoing single-arm crizotinib trials. Side effects of crizotinib mostly consist of grade 1-2 gastrointestinal events (nausea, vomiting, diarrhea and constipation), grade 1-2 edema and fatigue, grade 1 visual disorders, rare cases of elevated liver enzymes and pneumonitis (1.6%). Confirmatory trials comparing crizotinib to standard chemotherapy in upfront (ClinicalTrials.gov identifier: NCT01154140) and salvage (ClinicalTrials.gov identifier: NCT00932451) treatment settings of ALK-rearranged NSCLC are ongoing. It took an unprecedented rapid 4 years from the publication of the discovery of ALK-rearranged NSCLC in August 2007 to the conditional approval of crizotinib in August 2011.
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PMID:Crizotinib: a drug that crystallizes a unique molecular subset of non-small-cell lung cancer. 2231 63

Lung cancer in the pregnant woman is a very rare and dramatic coincidence with poor prognosis. Treatment depends on the gestational week of the pregnancy, patient's medical status, social, personal, familial, and even religious beliefs. We present a case of adenocarcinoma of the lung in a 34-year-old pregnant patient whose initial complaints were cough, dyspnea, fever and fatigue. She was diagnosed with pneumonia at another hospital, and antibiotic therapy was administered. Meanwhile, at 28 weeks she delivered a preterm low-birth-weight baby. Chest X-ray and thorax CT revealed a mass lesion in the upper left lung lobe. After admission to our clinic, needle aspiration of left supraclavicular lymph node and bronchoscopic biopsy from upper lobe bronchus showed a non-small lung cancer; adenocarcinoma. Brain MRI was normal. PET CT revealed multiple bone metastases. Multidisciplinary Tumor Committee at our hospital referred her to the Oncology Department as an advanced stage IV disease. Chemotherapy was administered with paclitaxel and carboplatin for a total of 12 weeks. Reassessment of the patient revealed new bone metastases and crizotinib was administered since her tumor was found positive for EML4-ALK mutations. The treatment was well tolerated. During a follow up period of 6 months her clinical condition was stable and no adverse events were encountered.
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PMID:Lung cancer and pregnancy. 2325 66

This paper presents an unusual case of gingival ALCL, which mimicked a benign hyperplastic lesion that occurred in a 57-year-old white man representing the first clinical manifestation of acquired immunodeficiency syndrome (AIDS). The patient was referred to the Dental Clinic of PUCPR complaining of a lobulated nodule on the gingiva of his upper central incisors. The presence of advanced chronic periodontitis and dental plaque raised suspicion for a benignancy. An excisional biopsy was performed, and large pleomorphic cells with an abundant cytoplasm, sometimes containing prominent nucleoli and "Hallmark" cells, were observed through hematoxylin and eosin staining. The tumor cells showed strong CD30 expression, EMA, Ki-67, and LCA, and negative stain for p80(NPM/ALK), CKAE1/AE3, CD20, CD3, CD56, and CD15. The final diagnosis was ALCL (ALK-negative). Further laboratory tests revealed positivity for human immunodeficiency virus (HIV). The patient was submitted to chemotherapy, but four months after diagnosis, the patient died due to pneumonia and respiratory failure. Oral anaplastic large-cell lymphoma (ALCL) is a rare disorder. Only 5 cases involving the gingiva have been reported, and to our knowledge, this is the first case reported of the ALCL, which mimicked a hyperplastic benignancy as the first clinical manifestation of AIDS.
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PMID:Gingival Anaplastic Large-Cell Lymphoma Mimicking Hyperplastic Benignancy as the First Clinical Manifestation of AIDS: A Case Report and Review of the Literature. 2384 Sep 74

Patients with advanced-stage or metastatic non-small cell lung cancer have a grim prognosis when first-line chemotherapy fails. Some cytotoxic drugs such as docetaxel and pemetrexed prolong overall survival by a few months, but at a cost of severe toxicity. Crizotinib (Xalkori*, Pfizer), a drug that inhibits ALK (among other tyrosine kinases) has been authorised for use in patients whose tumours overexpress this tyrosine kinase. Preliminary results of a comparative, randomised but unblinded trial in 347 patients suggest that crizotinib delays cancer progression and death more effectively than pemetrexed or docetaxel (median 7.7 months versus 3 months). However, it remains to be seen whether or not this translates into longer overall survival. Two uncontrolled trials including 136 and 119 patients also suggest that crizotinib delays tumour progression and death by about 8 months. Crizotinib is highly toxic, causing gastrointestinal, visual and hepatic disorders, cardiac arrhythmias (including QT prolongation) and pneumonia. These adverse effects were all more frequent than with docetaxel or pemetrexed. Some of these effects are more difficult to predict and manage than haematological disorders, which are the main adverse effects of docetaxel and pemetrexed. Crizotinib is extensively metabolised by cytochrome P450 isoenzymes and also inhibits P-glycoprotein, creating a risk of numerous pharmacokinetic interactions. Other interactions, with drugs that prolong the QT interval, may increase the risk of serious adverse effects. In practice, in patients with non-small cell lung cancer overexpressing ALK tyrosine kinase in whom first-line chemotherapy has failed, crizotinib appears to delay cancer progression and death, but at a cost of serious adverse effects. Further evaluation of crizotinib in well-designed comparative trials is needed before deciding whether or not to include it in the therapeutic arsenal.
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PMID:Crizotinib. 2442 36

On August 26, 2011, crizotinib received accelerated approval for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that is ALK-positive as detected by a test approved by the U.S. Food and Drug Administration (FDA). Approval was based on two single-arm trials demonstrating objective response rates (ORRs) of 50% and 61% and median response durations of 42 and 48 weeks. On November 20, 2013, crizotinib received regular approval based on confirmation of clinical benefit in study A8081007, a randomized trial in 347 patients with ALK-positive advanced NSCLC who had previously received one platinum-containing regimen. Patients were assigned (1:1) to receive crizotinib 250 mg orally twice daily or standard of care (docetaxel or pemetrexed). The primary endpoint was progression-free survival (PFS) determined by independent radiology review; secondary endpoints were ORR and overall survival (OS). PFS was significantly longer in the crizotinib arm, with median PFS of 7.7 and 3.0 months in the crizotinib and chemotherapy arms, respectively, and a 46% absolute increase in ORR but no difference in OS between treatment arms at the interim analysis. The most common adverse drug reactions (>25%) in crizotinib-treated patients were vision disorders, nausea, diarrhea, vomiting, constipation, edema, elevated transaminases, and fatigue. The most serious toxicities of crizotinib were hepatotoxicity, interstitial lung disease or pneumonitis, and QT-interval prolongation. Crizotinib's rapid clinical development program (6 years from identification of ALK rearrangements in a subset of NSCLC to full FDA approval) is a model of efficient drug development in this new era of molecularly targeted oncology therapy.
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PMID:FDA approval summary: crizotinib for the treatment of metastatic non-small cell lung cancer with anaplastic lymphoma kinase rearrangements. 2517 12

Ceritinib is a novel ALK inhibitor approved for advanced stage NSCLC with ALK gene rearrangement, progressed and/or intolerant to crizotinib. 13 patients were included in our study who received ceritinib. Majority of them were women and never smokers with a median age of 47 yrs. Nearly half of them had a compromised performance status and received ceritinib in third line and beyond. Ceritinib showed nearly 50% response rates. With a median follow up of 9 months for the entire cohort, median PFS and OS were not reached. However, the mean values for PFS and OS were 10.9 and 14.8 months,with an estimated 1 year PFS and OS being 56% and 78% respectively.1/3 of the patients had gastrointestinal and liver toxicities. Metabolic abnormalities were seen in 1/4 th of them. ceritinib was permanently discontinued in one patient due to pneumonitis. In conclusion, ceritinib has a favorable efficacy and side effect profile in our patient population., similar to that reported in large clinical trials. It has shown promising efficacy even in patients with compromised performance status; presence of brain metastases and heavily pre-treated disease.
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PMID:Ceritinib in anaplastic lymphoma kinase-positive nonsmall cell lung cancer among patients who were previously exposed to crizotinib: Experience from the Indian subcontinent. 2919 78

A previously healthy 44-year-old Japanese man with a 5-month history of lumbago presented to the emergency department with acute respiratory failure caused by pneumonia, and was immediately intubated. Computed tomography revealed a lung mass, pleural effusion, and multiple osteolytic lesions; however, the results of thoracentesis and bronchial brushing were not definitive. We performed a bone tumor biopsy guided by diffusion-weighted magnetic resonance imaging (DW-MRI) with mechanical ventilation, which enabled the diagnosis of ALK rearrangement-positive lung adenocarcinoma. In the era of precision medicine requiring proper biological tissue collection, DW-MRI was critical for identifying the biopsy site safely and with high precision.
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PMID:Diffusion-weighted magnetic resonance imaging-directed biopsy of a metastatic bone tumor: Lung adenocarcinoma with ALK rearrangement. 2997 88

Receptor tyrosine kinases (RTKs) bearing oncogenic mutations in EGFR, ALK and ROS1 occur in a significant subset of lung adenocarcinomas. Tyrosine kinase inhibitors (TKIs) targeting tumor cells dependent on these oncogenic RTKs yield tumor shrinkage, but also a variety of adverse events. Skin toxicities, hematological deficiencies, nausea, vomiting, diarrhea, and headache are among the most common, with more acute and often fatal side effects such as liver failure and interstitial lung disease (ILD) occurring less frequently. In normal epithelia, RTKs regulate tissue homeostasis. For example, EGFR maintains keratinocyte homeostasis while MET regulates processes associated with tissue remodeling. Previous studies suggest that the acneiform rash occurring in response to EGFR inhibition is a part of an inflammatory response driven by pronounced cytokine and chemokine release and recruitment of distinct immune cell populations. Mechanistically, blockade of EGFR causes a Type I interferon (IFN) response within keratinocytes and in carcinoma cells driven by this RTK. This innate immune response within the tumor microenvironment (TME) involves increased antigen presentation and effector T cell recruitment that may participate in therapy response. This TKI-mediated release of inflammatory suppression represents a novel tumor cell vulnerability that may be exploited by combining TKIs with immune-oncology (IO) agents that rely on T-cell inflammation for efficacy. However, early clinical data indicate that combination therapies enhance the frequency and magnitude of the more acute adverse events, especially pneumonitis, hepatitis, and pulmonary fibrosis. Further preclinical studies to understand TKI mediated inflammation and crosstalk between normal epithelial cells, cancer cells, and the TME are necessary to improve treatment regimens for patients with RTK-driven carcinomas.
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PMID:Linking tyrosine kinase inhibitor-mediated inflammation with normal epithelial cell homeostasis and tumor therapeutic responses. 3065 89

Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of poorly differentiated non-small-cell lung cancer (NSCLC), and no effective treatment is available in clinical practice currently. In the present report, a 61-year-old male patient was hospitalized due to cough, dyspnea, and right chest pain. Computed tomography (CT) showed spot- and piece-shaped shadows. The patient became very weak and had breathing difficulty after preliminary anti-pneumonia treatment with cefoperazone-sulbactam. Physical examination revealed dull sound by percussion and decreased breath sounds in the right lateral lung areas by auscultation. A second CT scan revealed a large amount of pleural effusion, and the patient was diagnosed with bloody pleural effusion through pleural space puncture. Multiple nodular lesions were found in the right pleural cavity under thoracoscopy. PSC was confirmed by biopsy and histopathology in combination with immunohistochemistry (IHC). Single-photon emission CT (SPECT) scan indicated multiple bone metastases. KRAS exon 2 mutation and EML4-ALK fusion were identified in carcinoma tissue by IHC and amplification refractory mutation system (ARMS)-PCR. The patient received one cycle of first-line combination chemotherapy of cisplatin and paclitaxel liposomes. However, the patient did not respond to the platinum-based combination chemotherapy within 3 weeks and was thus administered oral crizotinib instead of chemotherapy. Unfortunately, he still had rapid disease progression and died 2 weeks after the initiation of crizotinib treatment. Collectively, our results suggest that a PSC patient with coexistent KRAS mutation and ALK rearrangement would not benefit from chemotherapy and tyrosine kinase inhibitor (TKI) treatment.
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PMID:Poor prognosis of pulmonary sarcomatoid carcinoma with KRAS mutation and ALK fusion. 3111 83


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