Occurrence Of Solid Tumors Research Articles

Synchronous Head and Neck Squamous Cell Carcinoma and Hematologic Malignancies

Synchronous occurrence of solid tumors and hematological malignancy is a rare condition. There is no standard management or therapy for this complicated situation. The authors systematically reviewed articles searched using online databases. The patients are predominantly male, and the average age is similar to each malignancy. According to these studies, most patients are treated in order of aggressiveness. However, when a patient has multiple primary malignancies, all of which are aggressive, the treatment decision is challenging. Due to the limited number of cases, it is hard to have a firm conclusion about an optimal treatment policy. It appears that poor outcomes are mostly related to less adequate therapy. Because the condition is complicated in such cases and there is no standardized treatment, patients should be treated on an individual basis with treatments customized to a given patient’s particular circumstances. In addition, multidisciplinary communication and cooperation are crucial in the management of these patients. More in-depth research is still needed to reach a more conclusive treatment strategy and predictable outcomes.

The effects of cystine and theanine mixture on the chronic survival rate and tumor incidence of rats after total body X-ray irradiation†.

Cystine and theanine (CT), an amino acid mixture, provides the substrates cysteine and glutamic acid that promote glutathione synthesis. We previously reported that CT pre-treatment significantly improved the acute survival rate and reduced acute radiation injury of the small intestine and bone marrow of rats after 5Gy of total body X-ray irradiation. To examine the long-term effects of CT administration after irradiation, we investigated the effects of CT pre-treatment and pre- and post-treatment on the chronic survival rate and solid tumor (spleen, skin and subcutis, and thyroid) incidence after irradiation using 7-week-old male Wistar rats. CT pre-treatment of 280mg/kg was administered orally for 5 days before 5Gy irradiation, and CT pre- and post-treatment was administered 5 days before and 5 days after irradiation. A 0.5% carboxymethyl cellulose solution was administered as a control. The chronic survival rate of the pre-treated rats was higher than that of the control rats at 441 days after irradiation (40 vs 8.1%, P = 0.011). However, the survival rate did not significantly differ between the pre- and post-treatment and control rats at 467 days after irradiation (33.8 vs 30.2%, P = 0.792). In addition, more solid tumors, especially subcutis sarcomas, were observed in the pre-treatment rats (26.1%, 6/23) than in the control rats (4.5%, 1/22) after irradiation. Therefore, pre-administration of CT improves the chronic survival rate after irradiation; however, the occurrence of solid tumors was not suppressed.

A Case of Spontaneous Tumor Lysis After Pathologic Femur Fracture in Squamous Cell Lung Cancer.

Tumor lysis syndrome (TLS) occurs when large numbers of tumor cells lyse and release their contents, causing electrolyte derangements and renal injury. It is an uncommon complication of solid tumors and occurs most commonly after cytotoxic therapy rather than spontaneously. In this article, we describe a case of spontaneous TLS in a patient with squamous cell carcinoma of the lung. We also present a literature review of spontaneous TLS occurrence in solid tumors.

Multifunctional Biomimetic Nanovaccines Based on Photothermal and Weak‐Immunostimulatory Nanoparticulate Cores for the Immunotherapy of Solid Tumors (Adv. Mater. 9/2022)

Nanovaccines A cancer cell membrane@porous silicon nanoparticles@Au nanovaccine is developed by Zhenyang Luo, Hélder A. Santos, Bing Xia, and co-workers in article number 2108012, based on weak-immunostimulatory porous silicon@Au nanoparticulate cores and multi-antigenic cancer cell membranes. These exogenous nanovaccines boost antitumor immunity, preventing the occurrence of solid tumors, and significantly inhibiting the growth and metastasis of solid tumors after photothermal therapy combined with immune checkpoint inhibitors.

Multifunctional Biomimetic Nanovaccines Based on Photothermal and Weak-Immunostimulatory Nanoparticulate Cores for the Immunotherapy of Solid Tumors.

An alternative strategy of choosing photothermal and weak-immunostimulatory porous silicon@Au nanocomposites as particulate cores to prepare a biomimetic nanovaccine is reported to improve its biosafety and immunotherapeutic efficacy for solid tumors. A quantitative analysis method is used to calculate the loading amount of cancer cell membranes onto porous silicon@Au nanocomposites. Assisted with foreign-body responses, these exogenous nanoparticulate cores with weak immunostimulatory effect can still efficiently deliver cancer cell membranes into dendritic cells to activate them and the downstream antitumor immunity, resulting in no occurrence of solid tumors and the survival of all immunized mice during 55 day observation. In addition, this nanovaccine, as a photothermal therapeutic agent, synergized with additional immunotherapies can significantly inhibit the growth and metastasis of established solid tumors, via the initiation of the antitumor immune responses in the body and the reversion of their immunosuppressive microenvironments. Considering the versatile surface engineering of porous silicon nanoparticles, the strategy developed here is beneficial to construct multifunctional nanovaccines with better biosafety and more diagnosis or therapeutic modalities against the occurrence, recurrence, or metastasis of solid tumors in future clinical practice.

Revealing the BRD4-NOTCH3 fusion: A novel hill in the cancer landscape

ObjectivesGene fusions are becoming more evident in cancer scenario for either being the driver alterations, or for the great therapeutic target potential in many cases. Our aim was to characterize the BRD4-NOTCH3 fusion correlating with clinical features, and to determine the frequency of this fusion in the oncological population. Material and methodsOne patient diagnosed with lung adenocarcinoma at Hospital Sírio-Libanês (Brazil) was included. Foundation Medicine database was searched for all BRD4-NOTCH3 fusions among 233,804 specimens. ResultsA 76-year-old male patient was diagnosed with lung adenocarcinoma. Molecular assessments demonstrated negative ALK and EGFR, with PD-L1 expression positive by 60 %. He was treated with first line chemotherapy and second line immunotherapy. Subsequent treatments resume re-exposures to chemotherapy with poor responses. A next-generation sequencing (NGS) based assay was performed in the tumor biopsy, revealing mainly mutation in STK11, microsatellite stability, TMB-intermediate, MYC amplification and a BRD4-NOTCH3 fusion. The breakpoint analysis of this fusion indicates that BRD4 active domains are preserved, suggesting that it maintained DNA binding activity, as well as its capacity to be halt by BET inhibitors. Foundation Medicine database was searched for all BRD4-NOTCH3 fusions among more than 230-thousand specimens and it was found in 87 new cases in a rate of 0.04 % occurrence in solid tumors, predominately in gynecological cancers. The same rate was found when we analyzed a different dataset. ConclusionIn conclusion, this is the first report of the BRD4-NOTCH3 gene fusion associated with clinical characterization and, although rare, the occurrence of this fusion is constant in different population. Our data suggest that this fusion has great potential to targeted-therapy.

Tumor Lysis Syndrome after Hepatic Artery Embolization in a Patient with Neuroendocrine Tumor of Unknown Primary.

While tumor lysis syndrome is a relatively common oncologic emergency that may occur spontaneously or resulting from cancer directed therapy, it is relatively unusual occurrence in solid tumors, especially neuroendocrine tumors. It is also particularly rare after hepatic trans-arterial embolization. We report a case of a 60-year-old man who had hepatic trans-arterial embolization for metastatic neuroendocrine tumor of the liver of unknown primary, who developed tumor lysis along with post-embolization syndrome. He received aggressive intravenous fluid resuscitation, allopurinol and rasburicase for his tumor lysis syndrome but subsequently had acute renal failure for which he underwent renal replacement therapy. The patient responded well to treatment with complete resolution of his post-embolization syndrome, tumor lysis syndrome and acute renal failure. Our case report highlights the need to consider tumor lysis syndrome in solid tumors. It should be readily recognized and treated given the associated high risk of morbidity and mortality.

Solid Tumors in Post-Polycythemia Vera and Post-Essential Thrombocythemia Myelofibrosis: A Study on 2220 Patients

Solid Tumors in Post-Polycythemia Vera and Post-Essential Thrombocythemia Myelofibrosis: A Study on 2220 Patients

Abstract 383: Survey of spliceosome gene mutations and associated splicing defects across 33 cancer types

Abstract Hotspot mutations in the core spliceosome genes SF3B1, U2AF1, SRSF2 have been reported at high frequency in hematological malignancies and with lower occurrence in solid tumors. The TCGA Exome-seq and RNAseq data from 33 tumor types, the majority solid tumors, provides a unique opportunity to define the landscape of spliceosome mutations and associated splicing alterations in human malignancies. To this end, we compiled a list of 404 genes known to be involved in splicing. We performed 2 different mutational analyses; for the first analysis each tumor type was evaluated independently using MutSig2CV and 68 significantly mutated genes (q ≤ 0.1) were identified. The second analysis was performed by systematically looking for genes across all tumor types with loss of function (LoF) or hotspot in-frame mutations, which identified an additional 12 genes. Among the 80 genes, EEF1A1, HNRNPCL1, PCBP1, PHF5A and ZC3H4 carry hotspot mutations in addition to the previously reported spliceosome genes SF1, SF3B1, SRSF2 and U2AF1. Interestingly, we observed that known leukemia mutation/deletion near P95 in SRSF2 were also present in uveal melanoma. Furthermore, the 2 hotspot mutations in U2AF1 identified in leukemia and lung adenocarcinoma (LUAD) were detected in an additional 9 tumor types. We identified new SF3B1 hotspot mutations p.L833F, p.E862K, p.E902K/G, and p.R957Q located in the heat domains (HD) 9-12 in AML, bladder (BLCA), and endometrial cancers. Unexpectedly, alternative exon usage was the most common splicing event observed in p.E902K mutant BLCA samples. This observation differs from the reported alternative 3’ splice site usage induced by SF3B1 hotspot mutations located in the HDs 4-8. The majority of mutated spliceosome genes (52/80) contained LoF mutations across multiple tumor types. In particular, RBM10 showed the highest mutation frequency in LUAD (6.5%) and BLCA (3.8%), and FUBP1 in low grade glioma (8.0%). Differential splicing analysis comparing RBM10 LoF mutant and wild type LUAD identified exon inclusion and intron skipping as major splicing alterations, consistent with data showing RBM10 knock-down induces alternative exon usage within specific genes. Additionally, we identified cassette exon usage as the major splicing alteration in FUBP1 mutant versus wild type glioma samples. FUBP1 has been reported to bind and repress inclusion of AT rich exons, and confirming this finding we observed higher AT content in exons included in FUBP1 LoF mutant samples when compared to unaffected following exons. These findings suggest that LoF mutations in spliceosome genes impact splicing regulation and may play a critical role in cancer. In conclusion, the landscape of hotspot and LoF mutations in multiple spliceosome genes and associated splicing alterations highlight the increasing importance of the splicing machinery in tumorigenesis in solid tumors beyond hematological malignancies. Citation Format: Michael Seiler, Shouyong Peng, Anant Agrawal, Jennifer Tsai, James Palacino, Silvia Buonamici, Lihua Yu. Survey of spliceosome gene mutations and associated splicing defects across 33 cancer types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 383. doi:10.1158/1538-7445.AM2017-383

Solid Tumors in Patients with Chronic Lymphocytic Leukemia Who Received Frontline Lenalidomide Therapy: Distribution and Clinical Outcomes

Introduction: Patients (pts) with Chronic Lymphocytic Leukemia (CLL) are known to have an increased risk of other cancers. Treatment with lenalidomide has been associated with an increased rate of solid tumors (ST) in pts with multiple myeloma (MM). However, the occurrence of ST in patients with CLL receiving therapy with lenalidomide remains unknown.Methods: We evaluated the development of ST in pts with CLL that received front-line treatment with lenalidomide as monotherapy or in combination with rituximab in clinical trials conducted at our institution. We report the characteristics and timing of ST, as well as patient outcome. All pts enrolled had indication for therapy according to the International Workshop on CLL guidelines and no history of malignancy for three years, with the exception of treated malignancy with indolent behavior such as prostate cancer that was treated with surgery or radiation therapy.Results: One-hundred twenty-one pts were enrolled in two consecutive phase II clinical trials of frontline therapy with lenalidomide (N = 61, 51%) or combination of lenalidomide and rituximab (N = 60, 49%). Baseline pts characteristics are shown in Table 1, median age was 66 yrs and 24% of patients were age 70 or older. At a median follow up after lenalidomide therapy of 41 months (range 1-102+), 7 (6%) pts developed a ST: renal cell carcinoma (RCC, 3 pts), localized breast cancer (LCIS and DCIS, 2 pts), pancreatic adenocarcinoma (1 pt) and colon adenocarcinoma (1 pt) (details are shown in Table 2). The median time interval between receiving lenalidomide-based therapy and the development of ST was 1.5 years (range 0-8.5). At the time of this report, 5 out of 7 pts with ST are alive and cancer-free. Two pts died: 12 months and 18 months after developing ST from progression of pancreatic adenocarcinoma and heart failure, respectively.Since pts with CLL have a high rate of non-melanoma skin neoplasms (NMSC), we also monitored patients for new diagnoses of skin cancers. Seven (6%) additional pts developed NMSC, 4 of these pts had prior history of NMSC. All cases of NMSC were superficial and did not require systemic therapy.Additionally, because of the high median age of this population, we reviewed prior history of malignancies. Eleven (9%) pts had history of ST [prostate cancer (N = 9), bladder cancer (N = 1), RCC (N = 1)]. Twenty-two pts (18%) had skin cancers (NMSC, (N = 21) and 1 pt had history of melanoma. None of them had received chemotherapy, two had radiation therapy [prostate cancer = 1, NMSC (basal cell carcinoma of the nose (1 pt)]. All ST were in remission before starting therapy with lenalidomide for more than 3 years as per the inclusion criteria.Conclusions: Seven cases of ST were observed in our population of 121 pts with CLL that received initial therapy with lenalidomide, after a median follow-up of 3.5 years. The most common neoplasm was RCC followed by in-situ breast cancer. In our limited experience the timing, number and type of malignancies do not appear to mirror what was seen in patients with MM. However, this comparison may be limited by the size of our patient population and length of follow-up. Our group reported the incidence of ST in patients treated with FCR. After a similar follow-up the incidence of second malignancies was similar (5.9%), but the type of malignancies was different, although NMSC remained the most common ST in both experiences.Reporting the incidence of other malignancies in patients with CLL enrolled in large studies, including those of novel targeted agents, will help understanding the expected incidence of ST and how novel treatments modulate such risk. [Display omitted] [Display omitted] DisclosuresJain:Pharmacyclics: Consultancy, Honoraria, Research Funding; ADC Therapeutics: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Celgene: Research Funding; Seattle Genetics: Research Funding; Infinity: Research Funding; Abbvie: Research Funding; Genentech: Research Funding; Incyte: Research Funding; Servier: Consultancy, Honoraria; Novimmune: Consultancy, Honoraria; BMS: Research Funding; Novartis: Consultancy, Honoraria. Thompson:Pharmacyclics: Consultancy, Honoraria.

Epigenetic Therapy for Solid Tumors: Highlighting the Impact of Tumor Hypoxia.

In the last few decades, epigenetics has emerged as an exciting new field in development and disease, with a more recent focus towards cancer. Epigenetics has classically referred to heritable patterns of gene expression, primarily mediated through DNA methylation patterns. More recently, it has come to include the reversible chemical modification of histones and DNA that dictate gene expression patterns. Both the epigenetic up-regulation of oncogenes and downregulation of tumor suppressors have been shown to drive tumor development. Current clinical trials for cancer therapy include pharmacological inhibition of DNA methylation and histone deacetylation, with the aim of reversing these cancer-promoting epigenetic changes. However, the DNA methyltransferase and histone deacetylase inhibitors have met with less than promising results in the treatment of solid tumors. Regions of hypoxia are a common occurrence in solid tumors. Tumor hypoxia is associated with increased aggressiveness and therapy resistance, and importantly, hypoxic tumor cells have a distinct epigenetic profile. In this review, we provide a summary of the recent clinical trials using epigenetic drugs in solid tumors, discuss the hypoxia-induced epigenetic changes and highlight the importance of testing the epigenetic drugs for efficacy against the most aggressive hypoxic fraction of the tumor in future preclinical testing.

Bowel Imaging in IBD Patients: Review of the Literature and Current Recommendations

Imaging studies are essential in the diagnosis, treatment and follow up of IBD patients. The use of bowel imaging serves to confirm the diagnosis, assess disease extent and characteristics (inflammatory versus fibrostenotic) and complications. Accepted methods for bowel imaging in IBD patients are: CT enterography (CTE), MR enteropgaraphy (MRE), Abdominal ultrasound and capsule endoscopy. Each technique has its advantages and disadvantages. IBD patients have relatively high risk for colorectal cancer, small bowel cancer lymphomas and other malignancies. This risk is related to the chronic inflammatory process as well as to immunosuppressive therapy. Accumulating data shows that exposure to ionizing radiation elevates the risk for malignancy. Even exposure to relatively low doses of radiation as 50 mSv was shown to cause an increase in the occurrence of solid tumors, mainly colorectal cancer and urogenital malignancies. Individualized approach considering patients' symptoms, age, medical history, previous radiation exposure and malignancy risk as well as the local facilities and experience should guide physicians' decision regarding the preferred imaging modality.

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Introduction: Tumor lysis syndrome (TLS) is an oncologic emergency that refers to the constellation of deranged metabolic state, characterized by hyperkalemia, hyperphosphatemia, hyperuricemia, hypocalcemia, and/or azotemia, secondary to rapid breakdown of tumor cells. It is a life threatening emergency that typically follows administration of chemotherapy or rarely may be spontaneous. Tumor lysis syndrome is most commonly seen in the setting of a malignancy of high proliferative rate, large tumor burden and/or in a malignancy with high sensitivity to treatment. TLS is more prevalent in hematologic malignancies and is rarely noticed in solid tumors, with only total of 10 cases reported from year 1977-2011 in association with breast cancer. All the patients who develop this complication are critically ill and at a high risk of grave consequences including death as a result of this syndrome. Case: A 28-year-old woman at 28 weeks of pregnancy with a history of breast cancer was brought to the ER in status epilepticus. She was intubated for airway protection and admitted to Medical Intensive Care Unit for close monitoring. Patient had been diagnosed with biopsy proven invasive ductal carcinoma of her breast with ER/PR positivity and Her-2-neu negativity, two years ago. She was started on Tamoxifen which she took for a year before discontinuing it a year ago. She declined any treatment that she was offered and did not have any further follow up with her oncologist since a year prior to her presentation. On her current admission, patient was noticed to have extensive metastatic disease involving cranium, ribs, cervical, thoracic and lumbar spine with multiple intracranial and hepatic lesions as well. During her hospital course, while she was in the ICU and before she received any type of chemotherapy her blood work demonstrated worsening hyperuricemia, hyperphosphatemia and hypocalcemia. Patient's laboratory work up revealed a uric acid level of 12.1mg/dL, with phosphate of 4.1mg/dL and calcium ranging from 6.9 - 8.1mg/dL. In light of her laboratory results, patient met "Cairo-Bishop" definition of tumor lysis syndrome. She was closely monitored in the Medical-Intensive care unit and was started on allopurinol and aggressive fluid therapy. Patient responded well to this intervention and over the course, she had a rapid decline in her uric acid levels and normalization of other electrolyte derangement. Fortunately, she did not develop any cardiac arrhythmia or recurrent seizure episodes. Discussion: Tumor lysis syndrome is one of the most dreaded complications of aggressive malignancies but is extremely rare in untreated non-hematologic solid tumors. In literature, 370 cases have been reported of TLS in solid tumors of which only 10 cases in association with breast cancer. In the year 2004, Cairo-Bishop definition was proposed with specific laboratory criteria for the diagnosis of Tumor lysis syndrome and was defined as any two or more abnormal serum values of uric acid, potassium, phosphate or calcium in presence of adequate hydration and use of hypouricemic agents. Presentation of this individual is of value because TLS is a rare occurrence in solid tumors but clinicians should be aware of it so to be able to diagnose and aggressively treat it, as it is associated with a poor clinical course and is very commonly complicated by cardiac arrhythmias, renal failure, recurrent seizures or sudden death. Thus, it is recommended that all the patients who develop or are suspected to have tumor lysis syndrome deserve close monitoring and follow up in the intensive care unit.

Double Endocrine Neoplasia in a Renal Transplant Recipient: Case Report and Review of the Literature

Introduction The incidence of cancer compared for age groups is 3–4 times higher in transplant recipients than the general population. The increased risk is related to immunosuppressive therapy as well as the use of increasingly older donors and recipients. Although cardiovascular disease with a functioning transplant is the leading cause of death (47%), cancer mortality is significant especially among older patients. However, the most frequent posttransplantation cancers relate to hemolymphopoietic organs and skin, whereas the occurrence of solid tumors elsewhere is rare. Herein we have described a rare case of synchronous double malignancy of endocrine organs (thyroid-adrenal) in a young woman who underwent renal transplantation. Case Report A 37-year-old woman with end-stage renal disease for 18 years underwent transplantation when she was 30 years old with a 17-year-old standard cadaveric donor receiving immunosuppressive therapy with mycophenolate mofetil, cyclosporine, and steroids. Follow-up demonstrated good indices of renal function with negative tumor pathology at 79 months when, at an annual ultrasound monitoring, we found a lesion in the right lobe of the thyroid and left adrenal neoplasm of dubious interpretation. The cytology for the thyroid was highly suspicious of papillary carcinoma, whereas the histological examination after surgery diagnosed a thyroid multifocal papillary microcarcinoma (mpT1NxMx) and an oxyphil cell adrenocortical carcinoma (pT2, N0). Results Six months after total thyroidectomy with central lymphadenectomy and left kidney and adrenal gland removal the patient showed no evidence of recurrent lesions and stable graft function. Conclusions The rare occurrence of solid tumors after transplantation has no known etiopathogenetic relation. Despite the young age of the patient and the double neoplasm that could have produced an unfavorable outcome for the patient and the graft, careful follow-up for tumor pathologies and multidisciplinary management achieved an early diagnosis of both tumors with a surgical eradication without adjuvant therapy, preserving the life of the patient and the function of the graft.

The Spindle-Assembly Checkpoint, Aneuploidy, and Gastrointestinal Cancer

Genomic instability is a common occurrence in solid tumors, and it has long been conjectured that this process plays a causal role in cancer. The field of human molecular genetics has provided a means to test this hypothesis, fueled in part by the analysis of hereditary cancer-predisposition syndromes. Some of the first unequivocal support for the idea came from the discovery in 1993 that hereditary nonpolyposis colon cancer is caused by germline mutations of mismatch-repair genes.1,2 Work on the autosomal dominant hereditary breast and ovarian cancer predisposition syndromes, as well as on rare autosomal recessive syndromes such as Fanconi's . . .

The IGFR1 inhibitor NVP-AEW541 disrupts a pro-survival and pro-angiogenic IGF-STAT3-HIF1 pathway in human glioblastoma cells

Inappropriate activation of the IGF (insulin-like growth factor) system has been implicated in the growth and progression of a number of tumor types. Recent evidence indicates a possible role for the IGF system in modulating/mediating tumor cell response to hypoxia, a common occurrence in solid tumors, and particularly in malignant gliomas, causing tumor cells either to die, or to mount a pleiotropic adaptive response that is mainly orchestrated through activation of the hypoxia-inducible transcription factor HIF1. Experimental evidence suggests possible links between IGF- and HIF1-dependent signaling pathways, as well as a role for activated STAT3 in mediating their activities. Interestingly, igf2 is among the target genes transactivated by HIF1, thereby providing the missing link in a hypothetical autocrine self-amplifying circuit. The present study investigates the presence of the IGF-HIF1-VEGF axis in the human glioma cell line U-87 MG, and characterizes its molecular effectors. Our results show that exogenous IGF-I causes IGF1R and STAT3 activation, and increases HIF1α protein levels and HIF1 trascriptional activity, inducing VEGF release; a similar response, mediated by IGF-II release, is observed following HIF1α stabilization. The existence of an autocrine loop is confirmed by its down-regulation following inactivation of IGF1R (using the IGF1R-specific tyrosine kinase inhibitor NVP-AEW541), STAT3 (transfecting the cells with an expression vector encoding a dominant negative form of STAT3), or HIF1 (using the small molecule inhibitor YC-1). The ability of NVP-AEW541 to block this circuit could be beneficial in suppressing the growth and angiogenic potential of hypoxic glial tumors.

Nuclear Receptor-Induced Chromosomal Proximity and DNA Breaks Underlie Specific Translocations in Cancer

Chromosomal translocations are a hallmark of leukemia/lymphoma and also appear in solid tumors, but the underlying mechanism remains elusive. By establishing a cellular model that mimics the relative frequency of authentic translocation events without proliferation selection, we report mechanisms of nuclear receptor-dependent tumor translocations. Intronic binding of liganded androgen receptor (AR) first juxtaposes translocation loci by triggering intra- and interchromosomal interactions. AR then promotes site-specific DNA double-stranded breaks (DSBs) at translocation loci by recruiting two types of enzymatic activities induced by genotoxic stress and liganded AR, including activation-induced cytidine deaminase and the LINE-1 repeat-encoded ORF2 endonuclease. These enzymes synergistically generate site-selective DSBs at juxtaposed translocation loci that are ligated by nonhomologous end joining pathway for specific translocations. Our data suggest that the confluence of two parallel pathways initiated by liganded nuclear receptor and genotoxic stress underlies nonrandom tumor translocations, which may function in many types of tumors and pathological processes.

Multiple synchronous primary malignancies induced by benzene exposure: a case report

BackgroundChronic exposure to high concentrations of benzene is usually associated with the development of haematological diseases. However, solid tumors induced by benzene exposure are less frequent.Case presentationWe present an unusual case of triple synchronous primary malignancies most likely induced by occupational benzene exposure in a male patient. This spray painter was diagnosed as chronic aplastic anemia in his 21 years old after exposing to high concentration of benzene for three years. Then he was treated with glucocorticoid for four years. 40 years later, this patient developed three synchronous primary neoplasms with three different histologies including a basaloid squamous cell carcinoma of the esophagus, primary hepatocellular carcinoma, and well-differentiated squamous cell carcinoma of the gum.ConclusionThis case reminds us that the occurrence of solid tumors should be monitored in workers with occupational history linked with a high concentration exposure to benzene, though it's rarely happened.

Acute Tumor Lysis Syndrome in a Patient With Mixed Small Cell and Non-Small Cell Tumor

Tumor lysis syndrome, caused by massive tumor cell death, is an infrequent occurrence in solid tumors, and only a few cases of tumor lysis syndrome occurring in patients with lung cancer have been reported. We present a case of tumor lysis syndrome in a patient with mixed small cell and non-small cell lung cancer complicated by Listeria sepsis. Despite aggressive supportive measures with fluids, electrolytes, antibiotics, pressor agents, ventilation, and alkalinization of the urine, multiorgan failure developed, and the patient died on day 5 in the intensive care unit. Physicians should be aware of this infrequent but potentially fatal complication occurring in critically ill patients with bulky solid tumors so that early and aggressive therapeutic measures can be initiated and appropriate monitoring can be performed.

Solid tumors complicating Hodgkin's disease. A report on two patients with immunoglobulin deficiency

Multiple epithelial malignant neoplasms developed in two patients with Hodgkin's disease subsequent to radiotherapy and intensive chemotherapy. At the time of diagnosis, each patient also demonstrated a serum immunoglobulin deficiency. The significance of the occurrence of solid tumors in patients following therapy for Hodgkin's disease and the significance of cellular and humoral immunodeficiency in Hodgkin's disease in relation to second cancer development were studied. We suggest the establishment of a registry of leukemias and solid tumors developing in patients treated for Hodgkin's disease and other malignant neoplasms, possibly with detailed recording of immunocompetence data.