Amylase-producing lung cancer: case report and review of the literature

A case of hyperamylasemia with lung cancer is described. Macroamylasemia was excluded by a normal amylase/creatinine clearance ratio and by a sedimentation constant obtained by sucrose density gradient centrifugation. Positive immunofluorescent staining of tumor cells with a specific antibody against human salivary amylase and significant amylase activity in the primary tumor and metastases support the hypothesis of independent production of amylase by the lung tumor. Cellulose--acetate membrane electrophoresis demonstrated three bands of amylase activity. The major component corresponded to normal salivary amylase in electrophoretic mobility, isoelectric point and molecular size. The minor bands, one of which occupied about 10% of the total amylase activity in serum, urine and tissue homogenates, demonstrated a lower electrophoretic mobility and a more acidic isoelectric point. Gel filtration and electrophoresis disclosed that these minor bands were derived from an amylase isozyme with a larger molecular size than that of normal salivary amylase. The results suggest ectopic tumor production of heterogenous amylase isozymes, with the larger form being secreted into the circulation.     

Serum amylase is a sensitive tumor marker for amylase-producing small cell lung cancer?

A 68-year-old male smoker was diagnosed as having amylase-producing small-cell lung cancer (SCLC). The serum amylase level was elevated, at 1756 IU/l, and the isozyme pattern was salivary type. Serum levels of “the tumor markers” CEA and NSE were 10.0 ng/ml and 22.6 ng/ml, respectively, but the level of pro-GRP was within the normal range. He was treated with combination chemotherapy of carboplatin and irinotecan. After completion of the chemotherapy, the serum amylase level decreased below the cutoff range and a computed tomography (CT) scan of the chest revealed marked reductions of the tumor in the primary site and in the lymph node metastasis. In November 2003, he was noted to have a slightly raised amylase level, of 168 IU/l, and raised levels of tumor markers. At this time, a CT scan, bone scintigraphy, and magnetic resonance imaging (MRI) of the brain demonstrated no recurrence. However, in December, MRI of the brain showed multiple metastases, and the recurrence of SCLC was thus confirmed. For the treatment of disease progression, the same regimen of chemotherapy as that given initially was administered. CT imaging revealed a partial response in the primary site and lymph node metastasis, and the serum amylase level decreased to 91 IU/l. After the completion of the second chemotherapy regimen, he underwent cranial irradiation and further chemotherapy. However, unfortunately, he died owing to deterioration of lung cancer. In this patient, the serum amylase level was found to be a highly sensitive marker of lung cancer.     

Hyperamylasemia with papillary serous cystadenocarcinoma of the ovary

A case of a 49-year-old housewife with persistent hyperamylasemia, intractable amylase-rich ascites, and papillary serous cystadenocarcinoma of the ovaries is presented. The hyperamylasemia was attributable to neoplastic production of salivary-type isoamylase by analysis of isoamylase in the serum, urine, ascites, primary tumor of the ovaries and metastatic tumor of the lymph nodes. Cellular localization of amylase in the tumor tissues was demonstrated immunohistochemically in the primary and metastatic tumors using an indirect immunoperoxidase method.     

A case of amylase-producing ovarian tumor

A 51-year-old woman with ovarian carcinoma with hyperamylasemia is reported. She was admitted to Osaka General (JNR) Hospital in July 1982. A cystic tumor was palpated in the pelvis. Serum amylase, mainly the salivary type, in electrophoresis, had increased to 1583 Smith-Roe units/dL, while the pancreas was normal on ultrasonography and CT. Chemotherapy (MFC) was performed, and laparotomy revealed bilateral ovarian tumors. Histologically, they were serous cystadenocarcinoma. Serum and urinary amylase values dropped to the normal range after chemotherapy and surgery, and varied directly with the clinical course. Immunohistochemically, amylase was demonstrated in the tumor tissue by the PAP method. In conclusion, amylase was a useful marker in the diagnosis and follow-up of the present patient.     

A case of serous papillary cystadenocarcinoma of the ovary with hyperamylasemia

A case of serous papillary cystadenocarcinoma of the ovaries with hyperamylasemia has been studied immunohistochemically, electron microscopically, and biochemically. Cellular localization of amylase in the tumor tissue was determined by biochemical analysis, using an indirect immunoperoxidase method. Electron microscopy revealed electron-dense granules located in the peripheral region of the cytoplasm of most tumor cells.     

肺癌相关血清学肿瘤标志物研究进展

肿瘤生物标志物近年来一直是肿瘤基础和临床研究的一个十分活跃的领域.尽管迄今尚未找到肺癌特异性抗原,国内外研究人员已发现多种有潜力用于肺癌早期诊断、临床分型和分期、预后判断和疗效观察等的肿瘤生物标志.本文以癌胚抗原、神经元特异性烯醇化酶、细胞角蛋白19片段抗原、碳水化合物抗原242、粘蛋白1抗原、神经细胞粘附分子、组织多肽特异性抗原、干细胞因子、血管内皮生长因子、肝细胞生长因子、肺癌相关抗原和磷脂酰肌醇蛋白聚糖等为例,对肺癌相关血清学肿瘤生物标志物的研究进展作一综述.     

Ultrastructural, histochemical, and biochemical studies of two cases with amylase, ACTH, and beta-MSH producing tumor.

Two cases of intrathoracic tumor, different in histology and accompanied by hyperamylasemia, were studied ultrastructurally, histochemically, and biochemically. The ultrastructure of the tumor cell cytoplasm showed many zymogen granules in case 1 and smaller cored granules in addition to zymogen granules in case 2. Both tumors contained not only a large amount of amylase, which was electrophoretically of saliva type with three components, but also significant amounts of immunoreactive ACTH and beta-MSH. Starch film and immunofluorescence showed that the tumor cells stored amylase. It was concluded from these findings that the tumor cells ectopically producing amylase, which showed differentiation toward the cells with zymogen production, could differentiate toward the cells of ACTH-MSH system at the same time.     

Venous thrombosis and carcinoma of the lung: Case report and literature review

A case report of recurrent, migratory thrombophlebitis associated with lung cancer is presented. A detailed review of the pathophysiology of recurrent thrombophlebitis with lung cancer is done. The clinical implications and the need for an aggressive search for a primary lung tumor in patients presenting with this complication are stressed.     

Myasthenic syndrome (Eaton-Lambert syndrome) associated with pulmonary adenocarcinoma

A case of a 57-year-old man who presented with the clinical features of Eaton-Lambert syndrome preceding the diagnosis of lung adenocarcinoma at autopsy by 7 years, is reported. Although myasthenic syndrome is intimately associated with pulmonary small cell carcinoma, which connotes a grave prognosis, a small percentage of the tumor can be squamous cell carcinoma or adenocarcinoma, which may be resectable. Therefore, a continued search for evidence of intrathoracic neoplasm must be pursued following manifestations of myasthenic syndrome.     

支气管镜下肺活检联合导管吸引细胞学检查对周围型肺癌的诊断价值

目的:评价支气管镜下利用一次性导管吸引细胞学检查联合肺活检收集肺组织标本,观察该方法对在常规支气管镜下不能看到病灶的周围型肺癌患者的诊断价值.方法:回顾性分析2016年10月到2019年10月共138例胸部CT初诊,临床诊断怀疑为肺癌的患者,肺活检联合导管吸引或者单纯肺活检确诊共124例,分析比较两种方法对不同段支气管...     

Downregulation and growth inhibitory role of FHL1 in lung cancer

Four and a half Lin-11, Isl-1, Mac-3 (LIM) protein 1 (FHL1) has been linked to carcinogenesis. However, the role of FHL1 in lung cancer remains unclear and the detailed mechanism underlying its tumor suppressive role is poorly understood. The purpose of this study was to examine FHL1 expression in lung cancer patients and to investigate how it was associated with lung cancer cell growth. Immunoblotting and immunohistochemistry showed that FHL1 protein was downregulated in over 90% of 80 lung cancer patients. FHL1 expression was strongly correlated with tumor histological types (p < 10(-4) ) and the differentiation of the tumor (p = 0.002). FHL1 inhibited anchorage-dependent and -independent growth of human lung cancer cell lines. The inhibitory effects of FHL1 on lung cancer cell growth were associated with both the G1 and the G2/M cell cycle arrest concomitant with a marked inhibition of cyclin A, cyclin B1 and cyclin D as well as the induction of the cyclin dependent kinase inhibitors p21 (WAF1/CIP1) and p27 (Kip1). Direct intratumoral injection of an adenovirus expressing FHL1 dramatically suppressed the growth of A549 lung cancer cells in nude mice. Our data suggest that reduced expression of FHL1 may play an important role in the development and progression of lung cancer and that FHL1 may be a useful target for lung cancer gene therapy.     

非小细胞肺癌循环核酸的研究进展

对于肺癌患者临床前期和无症状期,临床诊断往往缺少最有效的无创性检测方法。非小细胞肿癌(NSCLC)患者血循环中核酸含量明显高于正常人,研究证实其抗酸来源于肿瘤细胞,并且与原发肿瘤有着结构或功能上的某些一致性,因此循环核酸对肿瘤的早期发现和早期诊断及治疗都具有重要价值。近年随着细胞分子生物学技术的发展,循环核酸的检测成为可能,这方面的研究也成为热点,本文综述国内外关于NSCLC的循环核酸研究进展。     

MicroRNA-204 plays a role as a tumor suppressor in Newcastle disease virus-induced oncolysis in lung cancer A549 cells

Tumor development and progression are closely associated with various microRNAs (miRNAs/miRs). We have previously shown that Newcastle disease virus (NDV) strain 7793 induces oncolysis in lung cancer. However, how NDV exerts its oncolytic effect on lung cancer remains to be investigated. The present study assessed the role of miR-204 in the NDV-induced oncolysis of lung cancer A549 cells by oncolysis induction in vitro. miR-204 was significantly upregulated in NDV-treated A549 cells. Overexpression or inhibition of miR-204 was significantly associated with NDV-induced oncolysis in A549 cells. Caspase-3 and Bax, major regulators of the apoptosis pathway, were regulated by miR-204, and the association between caspase-3-related apoptosis and miR-204 was identified in NDV-mediated oncolysis. These data demonstrated that miR-204 as a tumor suppressor played a role in NDV-induced oncolysis in lung cancer cells. The present study demonstrates the potential of strategies using miRs to improve oncolytic NDV potency, and highlights miR-204 as a tumor suppressor in NDV-induced oncolysis of lung cancer cells.     

Circulating mir-320a promotes immunosuppressive macrophages M2 phenotype associated with lung cancer risk

miRNAs play a central role in the complex signaling network of cancer cells with the tumor microenvironment. Little is known on the origin of circulating miRNAs and their relationship with the tumor microenvironment in lung cancer. Here, we focused on the cellular source and relative contribution of different cell types to circulating miRNAs composing our risk classifier of lung cancer using in vitro/in vivo models and clinical samples. A cell-type specific expression pattern and topography of several miRNAs such as mir-145 in fibroblasts, mir-126 in endothelial cells, mir-133a in skeletal muscle cells was observed in normal and lung cancer tissues. Granulocytes and platelets are the major contributors of miRNAs release in blood. miRNAs modulation observed in plasma of lung cancer subjects was consistent with de-regulation of the same miRNAs observed during immunosuppressive conversion of immune cells. In particular, activated neutrophils showed a miRNA profile mirroring that observed in plasma of lung cancer subjects. Interestingly mir-320a secreted by neutrophils of high-risk heavy-smokers promoted an M2-like protumorigenic phenotype through downregulation of STAT4 when shuttled into macrophages. These findings suggest a multifactorial and nonepithelial cell-autonomous origin of circulating miRNAs associated with risk of lung cancer and that circulating miRNAs may act in paracrine signaling with causative role in lung carcinogenesis and immunosuppression.     

肺癌干细胞与肺癌转移相关机制的研究进展

肺癌干细胞是来源于肺癌具有自我更新及多向分化潜能的一部分细胞群,被认为是肺癌发生发展的根源,其在肺癌转移过程中扮演重要角色,可能的作用机制主要包括上皮间质转化、肿瘤微环境、肿瘤血管生成、肿瘤耐药性、信号转导通路等几个方面.本文将对肺癌干细胞与肺癌转移相关机制做进一步探索,以期为防治肺癌转移提供新策略.     

Prevalence,clinicopathological characteristics,treatment, and prognosis of intestinal metastasis of primary lung cancer: A comprehensive review

AimLung cancer is mostly diagnosed at the advanced stage of disease. This review focused on prevalence, clinicopathological characteristics, treatment, and prognosis of intestine metastasis of primary lung cancer.MethodsPublished literature was searched using PubMed/Medline databases to extract studies on primary lung cancer metastasized to the intestine and then analyzed statistically.ResultsA total of 57 case reports and 3 retrospective studies were obtained from PubMed database. The prevalence of small bowel metastasis of primary lung cancer ranged between 2.6 and 10.7%. Histologically, poor tumor differentiation and advanced T and N stages of primary lung cancer associated with intestinal metastasis. Clinically, primary lung cancer metastasized to the intestine led to three frequent clinical presentations, i.e., intestine perforation, obstruction, and bleeding. The time interval between diagnosis of primary tumor and manifestation of intestinal metastasis ranged between 2 week and 4 years, while the time was within one year for 36 reported cases. 70% (45 of 63 cases) of patients did have an extra-intestinal metastasis at diagnosis of intestine metastasis. The median survival rate of 79 patients with follow-up data was 2.3 month and the old age, extra-intestinal metastasis, and intestine perforation were associated with poor prognosis.ConclusionThis study suggests that the primary lung cancer metastasized to the small bowel is not so rare as it is thought. Clinical management and treatment decision will be warranted and considered accordingly.     

Hyperamylasemia associated with lymphadenectomy in patients surgically treated for gastric cancer.

The influence of standard lymphadenectomy on the occurrence of damage to the pancreas was evaluated in 28 patients with gastric cancer, by analysing related serum and urine enzyme activities, pre- and postoperatively. Enzymatic evidence for pancreatic damage was related to the surgical procedure performed. Postoperatively, the patients treated by R2 gastrectomy had significantly increased levels of P-type amylase in the serum compared with findings in patients treated by R1 gastrectomy or bypass procedures. Conversely, the S-type amylase in both groups remained within normal limits during the study period. Pancreatic secretary trypsin inhibitor (PSTI) and phospholipase A2 (PLA2) proved to be less sensitive to pancreas damage caused by lymphadenectomy. The R2 patients with P-type hyperamylasemia had no major postoperative complications. Thus, while the standard R2 gastrectomy may well be a relevant factor associated with the occurrence of transient P-type hyperamylasemia, there seems to be no relation to major postoperative complications such as pancreatitis.     

循环肿瘤细胞在肺癌中的研究进展

循环肿瘤细胞(CTC)具有与肿瘤原发灶内一致的细胞学和基因遗传学特征。 已发现CTC与肺癌的生物学行为、治疗以及预后密切相关,有望成为肺癌的又一新标记物和治疗的新靶点。本文对CTC在肺癌中的研究进展作一综述。     

p53 Cooperates berberine-induced growth inhibition and apoptosis of non-small cell human lung cancer cells in vitro and tumor xenograft growth in vivo

Berberine has been shown to have anti-carcinogenic effects. Since p53 is the most commonly mutated tumor suppressor gene, and a lack of functional p53 is associated with an increased risk of cancer development, we examined the effects of berberine on p53-positive and p53-deficient non-small cell human lung cancer cells in vitro and in vivo. Treatment of A549, which express wild-type p53, and H1299, which are p53-deficient, human lung cancer cells with berberine resulted in inhibition of cell proliferation and an increase in apoptotic cell death; however, A549 cells were more sensitive to the berberine-induced cytotoxic effects than H1299 cells. Further, the treatment of A549 cells with pifithrin-alpha, a specific inhibitor of p53, or transfection of A549 cells with a p53 antisense oligodeoxynucleotide resulted in a reduction in the berberine-induced inhibition of cell proliferation and apoptosis. The berberine-induced apoptosis of both the A549 and H1299 human lung cancer cells was associated with the disruption of mitochondrial membrane potential, reduction in the levels of Bcl-2, Bcl-xl while increase in Bax, Bak, and activation of caspase-3. Treatment of the cells with pan-caspase inhibitor (z-VAD-fmk) or caspase-3 inhibitor (z-DEVD-fmk) inhibited berberine-induced apoptosis, thus suggesting the role of caspase-3. Further, the administration of berberine by oral gavage inhibited the growth of s.c. A549 and H1299 lung tumor xenografts in athymic nude mice, however, the growth of tumor xenograft of H1299 cells was faster than A549 cells in mice and the chemotherapeutic effect of berberine was more pronounced in the p53-positive-A549 tumor xenograft than p53-deficient-H1299 tumor xenograft.