NUT midline carcinoma as a primary lung tumor treated with anlotinib combined with palliative radiotherapy: a case report

Abstract Background NUT (nuclear protein in testis) midline carcinoma (NMC) is a rapidly progressive tumor arising from midline structures. Recent cases have reported that the poor prognosis with a median survival of 6.7 months and a 2 years overall survival of 19% due to limited treatment. Based on the effect of arotinib on inhibiting tumor growth and angiogenesis. We present one patient case treated with anlotinib and radiotherapy. Case presentation Here, we describe a 33-year old patient who complained of cough and chest pain and was diagnosed as a pulmonary NMC through CT scan, FISH and immunohistochemistry. In addition, we initially demonstrated that anlotinib combined with palliative radiotherapy could significantly prevent the tumor growth in a pulmonary NMC. Conclusion The report indicated that anlotinib combined with palliative radiotherapy could inhibit the tumor progression in a pulmonary NMC, which may provide a combined therapy to pulmonary NMC in the future.

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NUT Midline Carcinoma as a Primary Lung Tumor Treated With Anlotinib Combined With Palliative Radiotherapy: a Case Report

10.21203/rs.3.rs-202213/v1 ◽

2021 ◽

Author(s):

Jin Jiang ◽

Yikun Ren ◽

Chengping Xu ◽

Xing Lin

Keyword(s):

Tumor Growth ◽

Poor Prognosis ◽

Nuclear Protein ◽

Lung Tumor ◽

Combined Therapy ◽

Palliative Radiotherapy ◽

Patient Case ◽

Nut Midline Carcinoma ◽

Case Presentation ◽

The Poor

Abstract Background: NUT (nuclear protein in testis) midline carcinoma (NMC) is a rapidly progressive tumor arising from midline structures. Recent cases have reported that the poor prognosis with a median survival of 6.7 months and a 2 years overall survival of 19% due to limited treatment. Based on the effect of arotinib on inhibiting tumor growth and angiogenesis. We present one patient case treated with anlotinib and radiotherapy.Case presentation: Here, we describe a 33-year old patient who complained of cough and chest pain and was diagnosed as a pulmonary NMC through CT scan, FISH and immunohistochemistry. In addition, we initially demonstrated that anlotinib combined with palliative radiotherapy could significantly prevent the tumor growth in a pulmonary NMC.Conclusion: The report indicated that anlotinib combined with palliative radiotherapy could inhibit the tumor progression in a pulmonary NMC, which may provide a combined therapy to pulmonary NMC in the future.

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Cytological Features of a Variant NUT Midline Carcinoma of the Lung Harboring theNSD3-NUTFusion Gene: A Case Report and Literature Review

Case Reports in Pathology ◽

10.1155/2015/572951 ◽

2015 ◽

Vol 2015 ◽

pp. 1-5 ◽

Cited By ~ 4

Author(s):

Shiho Kuroda ◽

Shioto Suzuki ◽

Akira Kurita ◽

Mari Muraki ◽

Yoichiro Aoshima ◽

...

Keyword(s):

Case Report ◽

Nuclear Protein ◽

Lung Tumor ◽

Nut Midline Carcinoma ◽

Case Presentation ◽

First Case ◽

Cytological Features ◽

Pearl Formation ◽

Mitotic Figures ◽

First Time

Background. Nuclear protein in testis (NUT) midline carcinoma (NMC) is a very rare and aggressive malignancy. In more than two-thirds of these NMC cases, a fusion betweenNUTandBRD4orBRD3has been documented; other variants are rare. The cytology of NMC itself has been sparsely documented and that of variant NMC has never been reported.Case Presentation. A 36-year-old woman was admitted because of a rapidly progressing lung tumor with metastases to the breast and bone. We recently reported this patient as the first case of a variant NMC of the lung harboring anNSD3-NUTfusion, based on immunohistochemical and genetic analyses. Cytological material was available for the present review. A highly cellular smear contained a predominantly noncohesive pattern of monomorphic cells with diameters 2–2.5 times greater than those of small lymphocytes, with a round-to-oval nucleus, slightly irregular nuclear contours, variably prominent nucleoli, scant cytoplasm, and identifiable mitotic figures. Foci of stratification and overt pearl formation, including a dyskeratocyte, were occasionally observed. The necrotic background contained naked nuclei, karyorrhectic debris, apoptotic cells, and macrophages phagocytizing karyorrhectic debris; nuclear crushing was noted.Conclusion. The cytological features of a variant NMC of the lung are described for the first time.

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Mixed Signet-Ring and Transitional Cell Carcinoma of the Bladder. Report of a Case

Tumori Journal ◽

10.1177/030089169207800315 ◽

1992 ◽

Vol 78 (3) ◽

pp. 216-218

Author(s):

Jose I. Lopez ◽

Javier C. Angulo

Keyword(s):

Transitional Cell Carcinoma ◽

Cell Carcinoma ◽

Poor Prognosis ◽

Combined Therapy ◽

Transitional Cell ◽

Signet Ring Cell ◽

The Poor ◽

Signet Ring ◽

Ring Cell ◽

Carcinoma Of The Bladder

A case of transitional cell carcinoma of the bladder displaying prominent signet-ring cell features is reported. Despite combined therapy, the patient died within a few months of the diagnosis, thus confirming the poor prognosis of this tumor. We understand this entity could be considered as an example of neoplastic-associated metaplasia and therefore propose that it should be distinguished from genuine adenocarcinoma.

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The Pro-Survival Oct4/Stat1/Mcl-1 Axis Is Associated with Poor Prognosis in Lung Adenocarcinoma Patients

Cells ◽

10.3390/cells10102642 ◽

2021 ◽

Vol 10 (10) ◽

pp. 2642

Author(s):

Yu-Chu Su ◽

Yi-Cheng Chen ◽

Yau-Lin Tseng ◽

Gia-Shing Shieh ◽

Pensee Wu ◽

...

Keyword(s):

Tumor Growth ◽

Lung Adenocarcinoma ◽

Cancer Cells ◽

Cancer Patients ◽

Poor Prognosis ◽

Lung Tumor ◽

Embryonic Stem ◽

Physiological Role ◽

Stem Cell Marker ◽

Apoptosis Pathway

The embryonic stem cell marker Oct4 is expressed in several human cancers and is positively correlated with a poor outcome in cancer patients. However, its physiological role in cancer progression remains poorly understood. Tumor cells block apoptosis to escape cell death so that they can proliferate indefinitely, leading to ineffective therapy for cancer patients. In this study, we investigated whether Oct4 regulates the apoptosis pathway and contributes to poor prognosis in patients with lung adenocarcinoma. Our results revealed that Oct4 expression is correlated with Stat1 expression in lung adenocarcinoma patients and Oct4 is directly bound to the Stat1 promoter to transactivate Stat1 in lung adenocarcinoma cells. Expression of the Stat1 downstream gene Mcl-1 increased in Oct4-overexpressing cancer cells, while Stat1 knockdown in Oct4-overexpressing cancer cells sensitized them to cisplatin-induced apoptosis. Furthermore, Oct4 promoted Stat1 expression and tumor growth, whereas silencing of Stat1 reduced Oct4-induced tumor growth in human lung tumor xenograft models. Taken together, we demonstrate that Oct4 is a pro-survival factor by inducing Stat1 expression and that the Oct4/Stat1/Mcl-1 axis may be a potential therapeutic target for lung adenocarcinoma.

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Recombinant adeno-associated virus 9-mediated expression of Kallistatin suppresses lung tumor growth in mice

Current Gene Therapy ◽

10.2174/1566523220999201111194257 ◽

2020 ◽

Vol 20 ◽

Author(s):

Weihong Qu ◽

Jianguo Zhao ◽

Yaqing Wu ◽

Ruian Xu ◽

Shaowu Liu

Keyword(s):

Lung Cancer ◽

Gene Therapy ◽

Tumor Growth ◽

Lung Tumor ◽

Control Group ◽

High Dose ◽

Blank Control Group ◽

Adeno Associated Virus ◽

Tumor Tissues ◽

Subcutaneous Xenograft

Background:: Lung cancer remains the most common cause of cancer-related deaths in China and worldwide. Traditional surgery and chemotherapy do not offer an effective cure although gene therapy may be a promising future alter-native. Kallistatin (Kal) is an endogenous inhibitor of angiogenesis and tumorigenesis. Recombinant adeno-associated virus (rAAV) is considered the most promising vector for gene therapy of many diseases due to persistent and long-term transgen-ic expression. Objective:: The aim of this study was to investigate whether rAAV9-Kal inhibited NCI-H446 subcutaneous xenograft tumor growth in mice. Method:: The subcutaneous xenograft mode were induced by subcutaneous injection of 2×106 H446 cells into the dorsal skin of BALB/c nude mice. The mice were administered with ssrAAV9-Kal (single-stranded rAAV9) or dsrAAV9-Kal (double-stranded rAAV9）by intraperitoneal injection (I.P.). Tumor microvessel density (MVD) was examined by anti-CD34 stain-ing to evaluate tumor angiogenesis. Results:: Compared with the PBS (blank control) group, tumor growth in the high-dose ssrAAV9-Kal group was inhibited by 40% by day 49, and the MVD of tumor tissues was significantly decreased. Conclusion:: The results indicate that this therapeutic strategy is a promising approach for clinical cancer therapy and impli-cate rAAV9-Kal as a candidate for gene therapy of lung cancer.

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The Effect of Heterogenous Subregions in Glioblastomas on Survival Stratification: A Radiomics Analysis Using the Multimodality MRI

Technology in Cancer Research & Treatment ◽

10.1177/15330338211033059 ◽

2021 ◽

Vol 20 ◽

pp. 153303382110330

Author(s):

Lulu Yin ◽

Yan Liu ◽

Xi Zhang ◽

Hongbing Lu ◽

Yang Liu

Keyword(s):

Poor Prognosis ◽

Intratumor Heterogeneity ◽

Short Term ◽

Prognostic Information ◽

Manual Delineation ◽

Flair Sequence ◽

The Poor ◽

Contrast Enhanced ◽

Mri Sequences

Intratumor heterogeneity is partly responsible for the poor prognosis of glioblastoma (GBM) patients. In this study, we aimed to assess the effect of different heterogeneous subregions of GBM on overall survival (OS) stratification. A total of 105 GBM patients were retrospectively enrolled and divided into long-term and short-term OS groups. Four MRI sequences, including contrast-enhanced T1-weighted imaging (T1C), T1, T2, and FLAIR, were collected for each patient. Then, 4 heterogeneous subregions, i.e. the region of entire abnormality (rEA), the regions of contrast-enhanced tumor (rCET), necrosis (rNec) and edema/non-contrast-enhanced tumor (rE/nCET), were manually drawn from the 4 MRI sequences. For each subregion, 50 radiomics features were extracted. The stratification performance of 4 heterogeneous subregions, as well as the performances of 4 MRI sequences, was evaluated both alone and in combination. Our results showed that rEA was superior in stratifying long-and short-term OS. For the 4 MRI sequences used in this study, the FLAIR sequence demonstrated the best performance of survival stratification based on the manual delineation of heterogeneous subregions. Our results suggest that heterogeneous subregions of GBMs contain different prognostic information, which should be considered when investigating survival stratification in patients with GBM.

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Umbilical cord blood transplantation can overcome the poor prognosis of KMT2A-MLLT3 acute myeloid leukemia and can lead to good GVHD-free/relapse-free survival

Annals of Hematology ◽

10.1007/s00277-021-04413-2 ◽

2021 ◽

Author(s):

Juan Tong ◽

Lei Zhang ◽

Huilan Liu ◽

Xiucai Xu ◽

Changcheng Zheng ◽

...

Keyword(s):

Myeloid Leukemia ◽

Poor Prognosis ◽

Cord Blood Transplantation ◽

Chronic Gvhd ◽

Relapse Free Survival ◽

Free Survival ◽

Chemotherapy Group ◽

Blood Transplantation ◽

The Poor ◽

First Complete Remission

AbstractThis is a retrospective study comparing the effectiveness of umbilical cord blood transplantation (UCBT) and chemotherapy for patients in the first complete remission period for acute myeloid leukemia with KMT2A-MLLT3 rearrangements. A total of 22 patients were included, all of whom achieved first complete remission (CR1) through 1–2 rounds of induction chemotherapy, excluding patients with an early relapse. Twelve patients were treated with UCBT, and 10 patients were treated with chemotherapy after 2 to 4 courses of consolidation therapy. The 3-year overall survival (OS) of the UCBT group was 71.3% (95% CI, 34.4–89.8%), and that of the chemotherapy group was 10% (95% CI, 5.89–37.3%). The OS of the UCBT group was significantly higher than that of the chemotherapy group (P = 0.003). The disease-free survival (DFS) of the UCBT group was 60.8% (95% CI, 25.0–83.6%), which was significantly higher than the 10% (95% CI, 5.72–35.8%) of the chemotherapy group (P = 0.003). The relapse rate of the UCBT group was 23.6% (95% CI, 0–46.8%), and that of the chemotherapy group was 85.4% (95% CI, 35.8–98.4%), which was significantly higher than that of the UCBT group (P < 0.001). The non-relapse mortality (NRM) rate in the UCBT group was 19.8% (95% CI, 0–41.3%), and that in the chemotherapy group was 0.0%. The NRM rate in the UCBT group was higher than that in the chemotherapy group, but there was no significant difference between the two groups (P = 0.272). Two patients in the UCBT group relapsed, two died of acute and chronic GVHD, and one patient developed chronic GVHD 140 days after UCBT and is still alive, so the GVHD-free/relapse-free survival (GRFS) was 50% (95% CI, 17.2–76.1%). AML patients with KMT2A-MLLT3 rearrangements who receive chemotherapy as their consolidation therapy after CR1 have a very poor prognosis. UCBT can overcome the poor prognosis and significantly improve survival, and the GRFS for these patients is very good. We suggest that UCBT is a better choice than chemotherapy for KMT2A-MLLT3 patients.

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Kras-driven intratumoral heterogeneity triggers infiltration of M2 polarized macrophages via the circHIPK3/PTK2 immunosuppressive circuit

Scientific Reports ◽

10.1038/s41598-021-94671-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Theodora Katopodi ◽

Savvas Petanidis ◽

Kalliopi Domvri ◽

Paul Zarogoulidis ◽

Doxakis Anestakis ◽

...

Keyword(s):

Lung Cancer ◽

Tumor Growth ◽

Lung Tumor ◽

Quantitative Polymerase Chain Reaction ◽

Macrophage Polarization ◽

Metastatic Potential ◽

Intratumoral Heterogeneity ◽

M2 Macrophage

AbstractIntratumoral heterogeneity in lung cancer is essential for evasion of immune surveillance by tumor cells and establishment of immunosuppression. Gathering data reveal that circular RNAs (circRNAs), play a role in the pathogenesis and progression of lung cancer. Particularly Kras-driven circRNA signaling triggers infiltration of myeloid-associated tumor macrophages in lung tumor microenvironment thus establishing immune deregulation, and immunosuppression but the exact pathogenic mechanism is still unknown. In this study, we investigate the role of oncogenic Kras signaling in circRNA-related immunosuppression and its involvement in tumoral chemoresistance. The expression pattern of circRNAs HIPK3 and PTK2 was determined using quantitative polymerase chain reaction (qPCR) in lung cancer patient samples and cell lines. Apoptosis was analyzed by Annexin V/PI staining and FACS detection. M2 macrophage polarization and MDSC subset analysis (Gr1−/CD11b−, Gr1−/CD11b+) were determined by flow cytometry. Tumor growth and metastatic potential were determined in vivo in C57BL/6 mice. Findings reveal intra-epithelial CD163+/CD206+ M2 macrophages to drive Kras immunosuppressive chemoresistance through myeloid differentiation. In particular, monocytic MDSC subsets Gr1−/CD11b−, Gr1−/CD11b+ triggered an M2-dependent immune response, creating an immunosuppressive tumor-promoting network via circHIPK3/PTK2 enrichment. Specifically, upregulation of exosomal cicHIPK3/PTK2 expression prompted Kras-driven intratumoral heterogeneity and guided lymph node metastasis in C57BL/6 mice. Consequent co-inhibition of circPTK2/M2 macrophage signaling suppressed lung tumor growth along with metastatic potential and prolonged survival in vivo. Taken together, these results demonstrate the key role of myeloid-associated macrophages in sustaining lung immunosuppressive neoplasia through circRNA regulation and represent a potential therapeutic target for clinical intervention in metastatic lung cancer.

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