Hypertrophic osteoarthropathy associated with pulmonary tuberculosis

Hypertrophic osteoarthropathy is a syndrome frequently described in intrathoracic diseases, especially malignant ones. The association with lung tuberculosis is rarely reported. The authors describe the case of a 35-year-old patient, a smoker, hospitalised for lung cavitation associated with hypertrophic osteoarthropathy. The assessment of the aetiology was negative and the patient underwent lung surgery. The histopathological examination concluded as to chronic pulmonary tuberculosis. This report aims at alerting physicians about the possibility of hypertrophic osteoarthropathy in non malignant diseases, especially pulmonary tuberculosis which is still endemic in our country.     

Incidence of hypertrophic pulmonary osteoarthropathy associated with primary lung cancer

Background and objective: Although the association of hypertrophic pulmonary osteoarthropathy (HPO) with lung cancer was investigated in the 1960s, the recent incidence of clinically apparent HPO is not known. Data from a large series of patients with lung cancer were analysed, in order to assess the incidence of possible HPO, based on bone scintigraphy, as well as the incidence of clinically confirmed HPO. The clinical features of confirmed HPO were also evaluated. Methods: The medical records of patients admitted with lung cancer between January 1986 and August 2004 were reviewed. Bone scintigraphy showing symmetrical, abnormally high uptake in joints and/or long bones was considered to be suggestive of HPO. Patients who also had finger clubbing and joint pain were considered to have a confirmed diagnosis of HPO. Clinical histories and hormone levels were then investigated in these patients, to identify possible causal factors. Results: Among the 1226 lung cancer patients, 55 (4.5%) demonstrated abnormally high uptake on bone scintigraphy, suggesting possible HPO. Ten (0.8%) patients had clubbed fingers and joint pain and were eventually confirmed as having HPO. Serum hormone concentrations were abnormally high in the patients with confirmed HPO. Conclusions: This retrospective study indicated that 4.5% of lung cancer patients showed findings suggestive of HPO, a frequency similar to that reported previously. However, patients with HPO rarely showed the complete triad of signs. Although increased hormone concentrations may have caused the HPO, further investigation is required to confirm this.     

非小细胞肺癌伴对侧肺内结节的外科治疗

目的探讨非小细胞肺癌(non-small cell lung cancer,NSCLC)伴对侧肺结节的诊断及治疗。方法 24例获明确诊断的NSCLC患者伴对侧肺结节,均接受手术治疗,术后辅助放、化疗,并定期跟踪随访14～21个月。结果 24例患者中,其中6例有原发或转移癌;2例术后2年内死于心脑血管意外;16例良性病变;肺结节的大小,原发癌的病理类型和分期与结节性质之间无联系。结论 NSCLC患者伴对侧肺结节,若不能获得病理学诊断,并非手术禁忌证。     

血管形成与非小细胞肺癌

肿瘤血管形成是指从宿主现存血管内皮建立新生血管的过程。肿瘤的生长一般经历生长缓慢的血管前期和生长迅速的血管期。当实体肿瘤直径大于 1ｍｍ～ 2ｍｍ后 ,它的生长就必须依靠新生血管。新生血管为肿瘤提供营养物质和氧以及排出代谢废物 ,并为肿瘤细胞的播散提供最直接的通道[1] ,而且新生血管对肿瘤生长有旁分泌作用 ,即通过内皮细胞分泌生长因子刺激肿瘤生长[2 ] 。因此新生血管形成是肿瘤发生、发展中的关键环节之一。自 2 0世纪 90年代以来 ,肿瘤血管形成成为国外医学研究的热门话题 ,近几年来国内亦有学者开始关注这方面的研究。在…     

非小细胞肺癌患者放化疗后肺功能低下的相关性分析

目的分析非小细胞肺癌(NSCLC)患者放化疗后肺功能水平与其衰弱状态的相关性。 方法选择2020年5月至2021年12月我院收治的NSCLC放化疗患者69例为对象,根据放化疗后Fried衰弱表型分为无衰弱组11例、衰弱前期组26例、衰弱组32例。比较每组年龄、性别、BMI、病理类型、病理分期、Fried衰弱表型,检测每组放化疗后肺活量(VC)、第一秒用力呼气量(FEV₁)、用力肺活量(FVC)、一秒率(FEV₁/FVC)和分钟最大通气量(MVV),分析肺功能指标与放化疗后衰弱状态的相关性。 结果衰弱组年龄、病理分期高于无衰弱组及衰弱前期组(P<0.05);衰弱组Fried衰弱表型指标的发生率高于无衰弱组和衰弱前期组(P<0.05);衰弱组放化疗前VC%、FVC%、FEV₁%、FEV₁/FVC、MVV%低于无衰弱组和衰弱前期组(P<0.05),Logistic多因素分析肺功能指标与衰弱有相关性(P<0.05)。 结论NSCLC合并衰弱患者的VC%、FVC%、FEV₁%、MVV%水平低,可预测放化疗后的衰弱水平。     

Pulmonary hypertrophic osteoarthropathy associated with primary lung cancer]

The patient was a 61-year-old man admitted with the complaints of cough, arthralgia, and swelling of the legs. A chest roentgenogram and chest computed tomographic scan revealed a giant mass in the right upper lobe. Transperitoneal lung biopsy was performed, and a diagnosis of poorly differentiated adenocarcinoma was made. Physical examination confirmed swelling of the legs and clubbing of fingers on both hands. Bone scintigrams showed marked accumulation of 99 m-Tc-MDP in the long bones, bones of the hands, and patellae. These findings yielded a diagnosis of pulmonary hypertrophic osteoarthropathy associated with primary lung cancer. Although a high serum level of growth hormone was also detected, immunohistochemical analysis did not find growth hormone in the tumor itself. Chemotherapy and radiotherapy were performed but did not stop progression of the disease. The patient subsequently experienced worsening arthralgia and swelling of the legs. Steroid therapy rapidly alleviated the arthralgia and swelling, but not the clubbing of the fingers. Thereafter, the patient's serum CRP and ICTP dropped to normal levels, and the abnormal findings of bone scintigrams subsequently disappeared. The pulmonary hypertrophic osteoarthropathy was not clearly attributable to growth hormone. Steroid therapy was effective in this case. Bone scintigrams and serum CRP and ICTP may be useful indicators in the therapeutic follow-up and monitoring of patients with pulmonary hypertrophic osteoarthropathy.     

COPD合并非小细胞肺癌103例临床分析

目的 探讨COPD合并原发性非小细胞肺癌的临床特征.方法 分析我院近5年103例COPD合并非小细胞肺癌患者的临床资料.结果 COPD合并非小细胞肺癌多为有吸烟史男性老年人.103例患者中,鳞癌56.31%,腺癌34.95%.较常见的症状有咳嗽（86.41%）、咯血或痰中带血（54.37%）、呼吸困难（41.75%）等.胸部X线主要表现为肺门肿块（64.08%）、肺门和/或纵隔淋巴结肿大（24.27%）、阻塞性肺炎或肺不张（21.36%）.大多数患者经支气管镜检活检确诊（62.14%）.结论 COPD患者发生非小细胞肺癌风险高,如出现可疑肺癌征象,应尽早行相关检查.     

Role of selected endogenous peptides in growth hormone-releasing hexapeptide activity: analysis of growth hormone-releasing hormone, thyroid hormone-releasing hormone, and gonadotropin-releasing hormone.

The purpose of this study was to evaluate the contribution of endogenous GH-releasing hormone (GHRH) to exogenous GH-releasing hexapeptide (GHRP-6) activity, and to determine whether TRH or GnRH are endogenous analogs of GHRP-6. The activity of GHRP-6, a synthetic GH secretagogue, was significantly attenuated in rats administered GHRH antiserum or alpha-methyl-rho-tyrosine to reduce endogenous GHRH concentrations, and also in rats administered 5-50 micrograms/kg of [N-Ac-Tyr1,D-Arg2]-GRF 1-29 amide to block pituitary GHRH receptors. However, GHRP-6 activity was potentiated in rats administered 150 micrograms/kg [N-Ac-Tyr1,D-Arg2]-GRF 1-29 amide, presumably due to partial agonist activity of the GHRH receptor antagonist at the higher dose. These data show that endogenous GHRH contributes to full expression of exogenous GHRP-6 activity in vivo. Like TRH, a subthreshold dose of GHRP-6 was significantly more effective in hypothyroid rats than in euthyroid rats. However, suprathreshold doses of GHRP-6 were less effective in hypothyroid rats. Unlike TRH, GHRP-6 had no effect on GH and prolactin release from GH3 cells, and TRH and GnRH were poor competitors for 3H-GHRP-6 binding sites on pituitary membranes. A GnRH receptor antagonist did not block GHRP-6 activity in vivo, and GnRH administered alone or in combination with GHRP-6, did not stimulate GH release. The results of this study suggest that synergy between GHRH and GHRP-6 seen in pharmacological studies is physiologically relevant, and that TRH and GnRH are not endogenous analogs of GHRP-6.     

A vasoactive intestinal peptide antagonist inhibits non-small cell lung cancer growth.

The most prevalent lung cancer, non-small cell lung cancer (NSCLC) has receptors for vasoactive intestinal peptide (VIP). Here the effects of a VIP antagonist (VIP-hyb) on NSCLC growth were investigated. In vivo, when VIPhyb (10 micrograms, s.c.) was daily injected into nude mice, xenograft formation was significantly inhibited by approximately 80%. In vitro, VIP (100 nM) stimulated colony formation approximately 2-fold, whereas 1 microM VIPhyb inhibited colony formation by approximately 50% when adenocarcinoma cell line NCI-H838 was used. The attenuation of tumor proliferation is receptor mediated, as VIPhyb inhibited specific 125I-labeled VIP binding to cell lines NCI-H157 and NCI-H838 with an IC50 of 0.7 microM. VIP (10 nM) increased the cAMP levels 5-fold when cell line NCI-H838 was used, and 10 microM VIPhyb inhibited the increase in cAMP caused by VIP. Northern blot analysis and radioimmunoassays have shown VIP mRNA and VIP-like immunoreactivity in NSCLC cells. These data suggest that VIP may be a regulatory peptide in NSCLC and that VIPhyb is a VIP receptor antagonist that inhibits proliferation.     

Growth hormone-releasing hormone: an autocrine growth factor for small cell lung carcinoma

Antagonists of growth hormone-releasing hormone (GHRH) inhibit the growth of various cancers in vivo. This effect is thought to be exerted through suppression of the pituitary growth hormone-hepatic insulin-like growth factor I (IGF-I) axis and direct inhibition of autocrine/paracrine production of IGF-I and -II in tumors. However, other evidence points to a direct effect of GHRH antagonists on tumor growth that may not implicate IGFs, although an involvement of GHRH in the proliferation of cancer cells has not yet been established. In the present study we investigated whether GHRH can function as an autocrine/paracrine growth factor in small cell lung carcinoma (SCLC). H-69 and H-510A SCLC lines cultured in vitro express mRNA for GHRH, which apparently is translated into peptide GHRH and then secreted by the cells, as shown by the detection of GHRH-like immunoreactivity in conditioned media from the cells cultured in vitro. In addition, the levels of GHRH-like immunoreactivity in serum from nude mice bearing H-69 xenografts were higher than in tumor-free mice. GHRH(1-29)NH(2) stimulated the proliferation of H-69 and H-510A SCLCs in vitro, and GHRH antagonist JV-1-36 inhibited it. JV-1-36 administered s.c. into nude mice bearing xenografts of H-69 SCLC reduced significantly (P < 0.05) tumor volume and weight, after 31 days of therapy, as compared with controls. Collectively, our results suggest that GHRH can function as an autocrine growth factor in SCLCs. Treatment with antagonistic analogs of GHRH may offer a new approach to the treatment of SCLC and other cancers.     

Trichosanthin inhibits cell growth and metastasis by promoting pyroptosis in non-small cell lung cancer

BackgroundA number of studies have demonstrated that trichosanthin (TCS) can induce apoptosis in numerous types of tumor cell lines. However, whether TCS can induce pyroptosis has not yet been reported. This study aimed to investigate the role of TCS and its inhibitory effect on tumor growth by modulating pyroptosis in non-small cell lung cancer (NSCLC).MethodsEffects of different concentrations of TCS on the cell viability, proliferation, migration and invasion of NSCLC were detected by Cell Counting Kit-8 (CCK-8), colony formation, migration, and invasion assays. Immunofluorescence was used to detect the effect of TCS on the expression of pyroptosis marker protein gasdermin-D (GSDMD)-N in A549 cells. A tumor xenograft animal model was established by injecting A549 cells into nude mice.ResultsIn the present study, we found that TCS significantly inhibited the proliferation, migration, and invasion of A549 cells in a concentration-dependent manner. In addition, TCS at a high concentration (40 µg/mL) significantly promoted the expression of pyroptosis-related proteins [GSDMD-N, NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1, and GSDMD], which showed an inhibitory effect on the pyroptosis of A549 cells. Additionally, we found that necrosulfonamide (NSA) significantly reversed the inhibitory effect of high concentrations of TCS on the pyroptosis of A549 cells. The in vivo experiments showed that TCS effectively reduced the tumor volume and inhibited the expression of Ki-67, whereas it increased the expression of GSDMD-N.ConclusionsTaken together, these results indicated that TCS could inhibit the progression of NSCLC by promoting pyroptosis. These findings provide further information on the possible underlying mechanism of TCS in the treatment of NSCLC.     

Factors associated with long-term survival of patients with advanced non-small cell lung cancer

Background and objective: Only a small proportion of patients with advanced non‐small cell lung cancer (NSCLC) have a life expectancy greater than 2 years. The aim of this study was to identify the factors associated with long‐term survival of patients with advanced NSCLC. Methods: Patients who had received chemotherapy for stage IIIb or IV NSCLC that was not amenable to radiotherapy were studied retrospectively. Data were gathered prospectively from a comprehensive database. Long‐term survivors (>2 years) were compared with the other patients, with respect to clinical, biological and tumour–node–metastasis criteria. Results: Data for 245 consecutive patients were collected. Thirty nine patients (15.9%) survived for more than 2 years. Long‐term survivors were more likely to have had metastases at fewer sites (P = 0.008), an absence of bone metastases (P = 0.01), a performance status (PS) of 0–1 at first progression of the tumour (P = 0.002), a tumour that was controlled with first (P < 0.0001) and second‐line (P = 0.004) chemotherapy, maintenance therapy (P = 0.001), curative surgery (P < 0.0001), time to first progression of the tumour of >3 months (P < 0.0001), normal LDH levels at diagnosis (P = 0.049), and a haemoglobin concentration >110 g/L at first progression of the tumour (P = 0.02). In multivariate analysis, surgery, maintenance treatment, time to first progression of the tumour of >3 months, a PS of 0–1 at first progression, the number of chemotherapy agents received, and LDH levels, were significant predictors of long‐term survival. Conclusions: Assessment of these factors, and the use of maintenance therapy, when possible, may identify a population of patients with NSCLC that is likely to have a prolonged life expectancy.     

Multicenter cooperative observational study of idiopathic pulmonary fibrosis with non-small cell lung cancer

AIM: To research the natural course of idiopathic pulmonary fibrosis (IPF) with advanced non-small cell lung cancer (NSCLC) and the association between acute exacerbation (AE) of IPF and chemotherapy (CT). METHODS: From May 2007 through April 2011, 17 CT naive patients with IPF and advanced NSCLC were enrolled. Patients were classified into best supportive care (BSC) group or CT group based on the patient’s preference. Patients in the CT group received carboplatin (CBDCA) (AUC 5-6) plus paclitaxel (PTX) (175-200 mg/m²) on day 1 of each 21-d cycle as first-line therapy. RESULTS: All patients but one chose the CT group. In the CT group, the objective response rate was 38%. The most frequent toxicity ≥ grade 3 was neutropenia (88%). Two patients (12.5%) developed AE-IPF. The median progression-free survival, the median survival time and the 1-year survival rate were 4.1 mo, 8.7 mo and 35%, respectively. Second-line CT-related AE and CT-unrelated AE occurred in 2 and 3 patients (1: BSC group; 2: CT group), respectively. Seven (41%) of all patients developed AE-IPF throughout the clinical course, and 6 of 7 patients with AE-IPF died within one month. CONCLUSION: The incidence of AE-IPF was higher among IPF patients with advanced NSCLC than among those without NSCLC. CBDCA plus PTX regimen was tolerable and effective. However, AE-IPF has a fatal toxicity with or without CT in IPF patients with advanced NSCLC.     

非小细胞肺癌脑转移患者预后多因素Cox回归分析

目的探讨影响非小细胞肺癌(non-small cell lung cancer,NSCLC)脑转移患者生存时间的因素。方法回顾性分析我院收治的NSCLC脑转移并行头颅放疗患者302例,其中资料完整者171例进行分析。采用SPSS13.0统计软件行影响生存期的单因素及多因素Cox风险比例模型回归分析。探讨患者的临床特征及放疗方式等因素对患者生存期的影响。结果全组患者中位生存期为8.8(95%CI:7.2~10.3)个月;单因素分析显示:PS评分(P=0.002)、脑转移数量(P=0.023)、脑转移时间(P=0.031)、放疗方式(P=0.041)和肺癌是否切除(P=0.002)与患者预后有关;Cox多元回归分析显示:PS评分(P=0.04)和肺癌是否手术切除(P=0.04)为脑转移患者独立预后因素而与脑转移数量(P=0.65)、脑转移时间(P=0.71)、放疗方式(P=0.91)等因素无关。结论 NSCLC脑转移整体预后较差,手术切除肺部肿瘤且体力评分较好患者预后相对较好。