Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Stiff person syndrome (SPS) is a rare condition that causes rigidity in the muscles of the body and extremities, difficulty in walking, episodic spasms and progressive disability. SPS is generally seen together with autoimmune disorders such as diabetes mellitus, thyroiditis, vitiligo and pernicious anaemia. Rarely, it may develop as a paraneoplastic condition. SPS cases associated with breast cancer, small cell lung carcinoma, thymoma, Hodgkin's lymphoma and colorectal cancer have been reported in the literature. We present a case of a 58-year-old female patient who had malignant mesothelioma-associated SPS. Patients who have muscle spasms and difficulty in movement of joints should be evaluated for SPS before diagnosis of Parkinson's or other neurological disorders, and possible underlying malignancies should be excluded.
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PMID:The horses are the first thought but one must not forget the zebras even if they are rare: Stiff person syndrome associated with malignant mesothelioma. 2471 75

Ceritinib, also known as LDK-378 or Zykadia (Novartis), is a second generation inhibitor able to specifically target the anaplastic lymphoma kinase (ALK). In the last five years the interest for ALK small inhibitors grew rapidly, mainly because it was discovered that a small but significant percentage of non-small cell lung cancer (NSCLC) patients carries the oncogenic fusion protein EML4-ALK, in addition to about half percent of anaplastic large cell lymphoma (ALCL) patients, an aggressive but definitely rarer non Hodgkin's T cell lymphoma, and other malignancies. Moreover the first ALK inhibitor, crizotinib (Xalkori or PF02341066) was successfully approved for the treatment of late stages or metastatic ALK+ NSCLC, giving a new, safer therapeutic option for those patients. As predicted from previous clinical experience with other kinase inhibitors, crizotinib resistance inevitably occurred, so the clinical availability of new compounds able to overcome crizotinib resistance became a priority. Recently the first clinical data from the phase I trial on ceritinib were published (N Engl J Med 2014;370:1189-97): 59 patients were enrolled in the dose-escalation phase while additional 71 patients were treated in the following expansion phase. For 19 patients relapsed upon crizotinib treatment, ceritinib was used as second line therapy. Collectively, ORR was 58%, 56% for patients who received crizotinib before. Maximum tolerated dose (MTD) was established at 750 mg daily, but more than half patients had to reduce the drug dose because of adverse events. Finally PFS was 7.0 months. Here we discuss the clinical data presented in this article, comparing ceritinib with the first line inhibitor crizotinib and another second generation ALK inhibitor, alectinib (Chugai-Roche).
Transl Lung Cancer Res 2014 Dec
PMID:Ceritinib as a promising therapy for ALK related diseases. 2580 25

The blockade of immunological checkpoints has been successfully employed for the treatment of various solid neoplasms including melanoma, mesothelioma, non-small cell lung carcinoma, and renal cell carcinoma. A recent study indicates that the vast majority of patients with advanced, heavily pretreated Hodgkin's lymphoma (HL) also respond to a monoclonal antibody targeting programmed cell death 1 (PDCD1, best known as PD-1). Thus, checkpoint blockers may soon become part of our therapeutic armamentarium against hematological tumors. This would be particularly important as it would spare (at least some) patients the deleterious toxic effects of combinatorial chemotherapies and bone marrow transplantation. We anticipate that the realm of immunotherapy will eventually conquer vast portions of the territory that now belongs to hematological malignancies.
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PMID:Immunotherapy of hematological cancers: PD-1 blockade for the treatment of Hodgkin's lymphoma. 2615 25

Primary lung lymphoma (PLL) is a rare disease that comprises <0.5% of all primary lung tumors. It is defined as lymphoma confined to the lung with or without hilar lymph node involvement at the time of diagnosis or up to 3 months thereafter. Patients with PLL may be asymptomatic or manifest nonspecific clinical symptoms, for example, cough, chest pain, and dyspnea. Some individuals may be immunosupressed or have an autoimmune disorder. Radiologically, PLL can mimic pneumonia, lung carcinoma, or metastasis, and therefore, histologic confirmation is mandatory for definitive diagnosis. Primary lung marginal zone lymphoma of mucosa-associated lymphoid tissue type comprises 70% to 80% of cases. Less common B-cell lymphomas include diffuse large B-cell lymphoma, lymphomatoid granulomatosis (LyG), plasmacytoma, and other small lymphocytic lymphomas. PLLs of T-cell origin, largely represented by anaplastic large cell lymphoma, are extremely rare. LyG is an Epstein-Barr virus (EBV)-driven B-cell lymphoid neoplastic proliferation rich in T cells that produces vasculitis. The disease may present at different stages of progression. Differential diagnosis of PLL varies according to the lymphoma subtype: pulmonary mucosa-associated lymphoid tissue lymphoma should be distinguished from reactive inflammatory conditions, whereas high-grade lymphomas may resemble poorly differentiated lung carcinoma, metastatic disease, and other lymphomas. LyG can resemble inflammatory, infectious, and other lymphoid neoplastic processes. A panel of immunohistochemical markers, flow cytometry, and molecular methods are necessary to confirm the diagnosis in the majority of cases. In this article we review the clinical, radiologic, pathologic, and molecular characteristics of several B-cell and T-cell PLLs with exception of Hodgkin lymphoma and posttransplant lymphoproliferative disorder.
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PMID:Primary Pulmonary Lymphomas. 2645 11

Cancer involves so rarely the eye that it may be recognized late. The most frequent primary intra-ocular tumours are retinoblastoma in small children and uveal melanoma in adults. Vision loss in systemic cancer has a varied differential diagnosis. Uveal metastases are most often associated with breast cancer, but can herald lung carcinoma. Masquerade syndrome looks like inflammation but represents the ocular involvement of primary CNS non-Hodgkin lymphoma. Systemic cancer drugs, as well as radiotherapy, can cause ocular toxicity, mostly at the retina. In the rare paraneoplastic syndromes, patient's cancer antibodies cross-react with retinal antigens, leading to severe vision loss. When cancer involves the eye, a fast referral into specialized care can significantly improve visual and vital prognosis.
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PMID:[The eye and cancer]. 2685 56

After decades of setbacks, cancer immunology is living its Golden Age. Recent advances in cancer immunology have provided new therapeutic approaches to treat cancer. The objective clinical response observed in patients treated with antibodies that block the immune checkpoints, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell-death protein 1 (PD-1)/programmed cell-death 1 ligand 1 (PD-L1) pathways, has led to their FDA approval for the treatment of melanoma in 2011 and in 2014, respectively. The anti-PD-1 antibody nivolumab has received the FDA-approval in March 2015 for squamous lung cancer treatment. In addition, antibodies targeting PD-1 or PD-L1 have demonstrated their efficacy and safety in additional tumors, including non-small cell lung carcinoma (NSCLC), renal cell carcinoma (RCC), bladder cancer, and Hodgkin's lymphoma. Almost at the same time, the field of adoptive cell transfer has exploded. The chimeric antigen receptor (CAR) T technology has provided strong evidence of efficacy in the treatment of B cell malignancies, and different T cell based treatments are currently under investigation for different types of tumors. In this review we will discuss the latest advances in cancer immunology and immunotherapy as well as new treatments now under development in the clinic and potential strategies that have shown promising results in preclinical models.
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PMID:Advances in cancer immunology and cancer immunotherapy. 2701 Oct 48

Adult-onset opsoclonus-myoclonus syndrome (OMS) has been associated with multiple cancers, most commonly small-cell lung carcinoma and breast adenocarcinoma. A 53-year-old woman who presented with OMS was found to have primary central nervous system (CNS) diffuse large B-cell lymphoma. OMS has been described in only 5 cases with non-Hodgkin lymphoma (NHL), and this is only the third reported case of OMS in NHL limited to the CNS. Although the paraneoplastic antibody panel was negative, we presume that the OMS was a paraneoplastic manifestation. Antineoplastic and anti-immune therapy had no effect on the neurologic manifestations.
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PMID:Opsoclonus-Myoclonus Syndrome in Primary Central Nervous System Lymphoma. 2702 9

In some patients with suspected de novo or recurrent lymphoma, the absence of a palpable mass or peripheral lymph node enlargement can be a diagnostic challenge. We report our experience of fine needle aspiration (FNA) and biopsy in the management of 47 consecutive patients investigated in our institution over a period of 4 years. Lymphoma was suspected in 32 cases, and recurrent disease in 15 cases. Cytology was performed in all patients and biopsy in 16 patients, when a safe approach was possible. The specimens were obtained with computed tomography guidance and were diagnostic by cytology in 85% of cases: 28 patients had a newly diagnosed lymphoma and 3 had recurrent disease; residual fibrosis was diagnosed in 2 cases. Five patients with a previously diagnosed lymphoma had a new neoplasm: lung carcinoma: 3, renal adenocarcinoma: 1, metastatic lymph nodes: 1. One patient had non-neoplastic intercurrent disease (pulmonary nocardiosis). In 7 patients, no conclusive tissue was obtained (acellular: 1, blood: 3, necrosis: 3). In one case of suspected recurrent disease, a false-positive result was obtained. Cytology always allowed distinction between non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD), with attempts to subclassify NHL according to the International Working Formulation. In 12 patients, immunochemical studies could be performed for immunologic subclassification of lymphoma on the basis of cytology (n = 6) and biopsy (n = 6). Our results show that percutaneous fine needle aspiration cytology is a reliable method for the diagnosis and classification of lymphoma, and immunologic studies can be performed on cytology alone if biopsy is unsafe.
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PMID:Percutaneous Fine Needle Aspiration Cytology and Biopsy in the Diagnosis and Classification of Lymphoma: Clinical Evaluation. 2746 45

PD-1 and its ligands have been shown to play a significant role in evasion of malignant tumour cells from the immune system. Last year, the Unites States Food and Drug Administration (FDA) approved anti-PD-1 inhibitors for treatment of non-small cell lung carcinoma and recently expanded the use of immunotherapy for metastatic urothelial cell carcinoma and Hodgkin lymphoma. However, studies on expression of PD-1 and its ligand in malignant bone and soft tissue sarcoma are sparse. In this study, we evaluated PD-1 and PD-L1 expression on variants of liposarcomas and rhabdomyosarcomas, osteosarcomas and chondrosarcomas. Tissue microarrays (TMAs) for liposarcomas (well differentiated, myxoid/round cell, and pleomorphic), rhabdomyosarcomas (alveolar, embryonal, pleomorphic, and spindle cell), conventional osteosarcomas and chondrosarcomas were stained for PD-1 and PD-L1 antibodies. Adipose tissue, skeletal muscle, bone, osteochondroma and lipoma were used as control and benign counterparts. Western blot was performed to evaluate expression of PD-1 and PD-L1 in four sarcoma cell lines. Osteosarcomas, chondrosarcomas, and all variants of liposarcomas and rhabdomyosarcomas over-expressed PD-1 relative to normal tissue. Expression of PD-1 in rhabdomyosarcomas was associated with higher tumour stage. Only one case of pleomorphic liposarcoma, one case of pleomorphic rhabdomyosarcoma and two cases of alveolar rhabdomyosarcomas were positive for PD-L1. Normal adipose tissue, skeletal muscle, and bone were negative for both PD-1 and PD-L1 and lipomas and osteochondroma weakly expressed PD-1 but not PD-L1. Western blot confirmed the presence of PD-1 protein in all four sarcoma cell lines. Overall, our results showed cytoplasmic expression of PD-1 in the bone and soft tissue sarcomas, while PD-L1 was negative. Whether these data are an indication for effectiveness of immunotherapy in the management of malignant bone and soft tissue sarcomas remains to be elucidated.
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PMID:PD-1 and PD-L1 expression in bone and soft tissue sarcomas. 2868 24

Immune checkpoint inhibitors are the most striking innovation in the clinical development of immunotherapy. Monoclonal antibodies (mAbs) restore and augment the antitumor immune activities of cytotoxic T cells by mainly blocking immune checkpoint molecules on T cells or their ligands on antigen-presenting and tumor cells. Based on preclinical data, many clinical trials have demonstrated the acceptable safety profiles and efficacies of mAb in various cancers. The A first-in-class approved immune checkpoint inhibitor is ipilimumab, which is a fully humanized mAb that blocks the immunosuppressive signal by cytotoxic T-lymphocyte antigen 4. In 2011, the US Food and Drug Administration approved the use of ipilimumab for the treatment of advanced metastatic melanoma. Then, nivolumab, which is a humanized mAb that blocks programmed death-1 (PD-1), was approved for use in the treatment of advanced melanoma in 2014 and of advanced non-small-cell lung carcinoma (NSCLC) in 2015 in Japan. Pembrolizumab, which is another anti-PD-1 antibody, was approved for use in the treatment of advanced melanoma and advanced NSCLC as the first-line therapy in 2016 in Japan. Thereafter, nivolumab was also approved for use in the treatment of advanced renal cell cancer in August 2016, of Hodgkin's lymphoma in December 2016, and of head and neck cancer in March 2017 in Japan. Moreover, phase III trials of anti-PD-1 mAb and anti-PD-ligand 1 mAb for use in the treatment of cancers, such as gastric, ovarian, bladder, and esophageal cancers, are ongoing. Several clinical trials have investigated new agents, alone and in combination, for use in the treatment of various cancers. Current advances in tumor immunology have unveiled the importance of immunosuppressive cells, such as regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages, especially in a tumor microenvironment (TME). Some data from basic research in mouse models and the immunomonitoring of cancer patients suggest that the inhibition of immunosuppressive cells and the cytokines related to them activate and infiltrate cytotoxic T cells and in TME, which could be one of the next combination strategies. The current clinical development of, translational research on, and future challenges in utilizing immune checkpoint inhibitors are described.
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PMID:Development of immune checkpoint inhibitors. 2888 82


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