Large Cell Carcinoma Research Articles

Well-differentiated neuroendocrine tumors of the lower urinary tract: biologic behavior of a rare entity

The spectrum of neuroendocrine (NE) tumors in the genitourinary tract ranges from the aggressive large and small cell carcinomas to the often benign paraganglioma and well-differentiated neuroendocrine tumor (WD-NET). At least 15 pure lower urinary tract (LUT) WD-NETs have been described. Owing to the rarity of WD-NET in the LUT and the limited number of reported cases, a better definition of their biologic long-term behavior is warranted. Herein, we aim to describe 10 new cases of WD-NET arising in the LUT and expand on follow-up findings. Ten consultationcases were identified and included 6 men and 4 women who ranged from 45 to 73 years of age. Seven cases arose in the bladder with one located in the bladder neck, 1 arose in the prostatic urethra, 1 arose in the female urethra, and 1 arose in the left ureteral orifice. All lesions were confined to the lamina propria, and tumor architecture was pseudoglandular in all cases. Associated cystitis cystica et glandularis was identified in 5 cases; urothelial papilloma and florid von Brunn's nests were found in 2 additional cases. Immunohistochemical staining for synaptophysin and chromogranin was diffusely positive in 9 cases and focal in 1 case, and the Ki-67 proliferation index was 5% or less in all tumors. Follow-up ranged from 37 to 137 months (mean = 82; median = 77), and there was no evidence of residual disease or recurrence in any of the 10 patients during the follow-up period.

Druggable driver gene alterations in redefined large cell carcinoma in Chinese patients: an observational study.

BackgroundFew reports have investigated the genetic status of large cell carcinoma (LCC) in Chinese patients under the 2015 World Health Organization (WHO) classification. We aimed to analyze the distribution of druggable driver gene alterations, including mutations in epidermal growth factor receptor (EGFR), Kirsten rat sarcoma 2 viral oncogene homolog (KRAS), proto-oncogene B-Raf (BRAF), and phosphatidylinositol-4,5 biphosphate 3-kinase catalytic subunit alpha (PIK3CA) and translocations in echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) and ROS proto-oncogene 1 (ROS1), in a large population of patients with LCC under the 2015 WHO classification, and to assess the clinical outcomes of patients with LCC harboring these genetic alterations.MethodsA cohort of 322 patients with LCC resected between June 2015 and December 2018 was included in this study. The clinical characteristics of the patients and data on the distribution of EGFR, KRAS, BRAF, PIK3CA, EML4-ALK, and ROS1 alterations were retrospectively collected. The disease-free survival (DFS) of patients with LCC was analyzed using the log-rank test.ResultsAmong the patients with redefined LCC, the proportion of males was much higher than that of females. Detection of LCC was more frequent in patients >60 years of age (71.4%). Mutations of EGFR were found in 3.6% of the LCC participants, predominantly in non-smokers. Mutations in KRAS were observed in 7.8% of the LCC patients, mainly in males and smokers. Mutations in PIK3CA and EML4-ALK translocations comprised 2.1% and 0.52% of the identified alterations, respectively. No alterations were identified in ROS1 and BRAF. After molecular stratification, no significant difference in DFS was identified between wild-type (WT) and mutation groups (29.91±3.83 vs. 25.33±6.04 months, P=0.48).ConclusionsUnder the 2015 WHO criteria, LCC was more frequently detected in elderly male patients with inferior prognoses. The frequency of EGFR and KRAS mutations was found to be the highest. Mutations in EGFR occurred more frequently in non-smokers, whereas KRAS mutations occurred predominantly in males and smokers. The PIK3CA mutations and EML4-ALK translocations were rare in patients with LCC. Our data revealed that the identification of clinically actionable molecular alterations in LCC may help guide personalized cancer treatment decisions in the future.

Trends, and tumor characteristics of lung cancer and malignant pleural mesothelioma in the East of Libya

Background: Lung cancer is the most common cancer worldwide and the leading cancer killer. Lung cancer is classified histologically into two types; small-cell lung cancer and nonsmall-cell lung cancer (NSCLC) (squamous cell carcinoma, adenocarcinoma (AC), large cell carcinoma [LCC]). Malignant pleural mesothelioma is a rare thoracic tumor. We aimed to provide comprehensive epidemiological data about lung cancer in the eastern part of Libya. Patients and Methods: A retrospective medical records review of lung cancer patients attending the oncology department of Benghazi Medical Center from January 1, 2006 to December 31, 2015. Results: There were 684 lung cancer cases out of 7725 total registered cancer cases (8.85%), 627 were male (91.7%, median age 63.5), and 57 females (8.3%, median age 64). NSCLC was the dominant histology 78.5%, SCLC 11%, and malignant mesothelioma 2.5%. NSCLC subtypes were AC (35.1%), squamous carcinoma (25.7%), LCC (4.6%), and not otherwise specified (12.6%). Only 30.6% of cases were diagnosed in Libya, the most commonly used diagnostic modalities were bronchoscopic biopsy 46.6%, and computed tomography guided biopsy 17.4%. Only 18 cases were tested for epidermal growth factor receptor sensitizing mutations and anaplastic lymphoma kinase rearrangement fusion. Stage IV was the most common initial stage for NSCLC 60%, malignant mesothelioma 47.1%, and 74.7% of SCLC presented with extensive disease. Only 42.9% of males and 5.3% of female lung cancer patients were smokers. Conclusions: Lung cancer is a major health burden in Libya, and it is increasing in incidence; this epidemiological study tries to put this problem into public health and clinical perspective.

Reconstruction of Large Nasal Alar Squamous Cell Carcinoma Defect Using a Superiorly - Based Nasolabial Flap

The nasal skin is the most common site of malignancy in the face accounting for as much as 25.5 percent by virtue of its location and propensity for direct exposure to ultraviolet radiation from the sun.1-3 Among the various cutaneous malignancies, basal cell carcinoma is the most ommon, but other types of cancer such as squamous cell carcinoma, cutaneous malignant melanoma, and basosquamous carcinoma are also common.4 Following surgical resection of a malignant lesion, the defect calls for a reconstructive option that will restore aesthetics and function. We present a squamous cell carcinoma of the nasal alar skin which underwent excision and reconstruction of the defect using a superiorly - based nasolabial flap.
 CASE REPORT
 A 66-year-old man consulted at the outpatient clinic due to a nasal alar mass on the right. The mass started one year prior to consult as a pimple-like lesion on the right nasal ala. There was no history of manipulation or trauma to the aforementioned area. He consulted at a local hospital where he was given unrecalled antibiotics that did not cure the lesion. Instead, he noticed that it gradually enlarged, and a deep ulceration developed within the mass. This prompted consult at our outpatient clinic where a 3 x 2 cm ulcerating mass with crusting and necrotic areas was noted on his right nasal ala. (Figure 1) Anterior rhinoscopy showed an intact mucosa in the right nostril with no gross evidence of tumor involvement. There were no enlarged cervical lymph nodes palpated in the neck. A wedge biopsy revealed a well-differentiated squamous cell carcinoma. He claimed that he had no family history of cutaneous malignancy. However, he had a 20 pack-year history of smoking and was a heavy alcoholic beverage drinker. He previously worked as an electrician and denied chronic exposure to sunlight.
 He consequently underwent excision of the right nasal alar mass with 5-mm margin. (Figure 2A, B) A histologic evaluation of the margins revealed that the borders and tumor base were negative for malignancy. The alar cartilage was not involved by tumor. Reconstruction of the defect was done using a superiorly - based nasolabial flap on the right. (Figure 3A, B, C) Two weeks postoperatively, the patient came in for follow-up with a healed, aesthetically - pleasing, and well-coaptated wound. (Figure 4) He remains free of any evidence of recurrence after 1 year.

Removal of an unusually large squamous cell carcinoma of the scalp with calvarial invasion: a multifaceted reconstructive nightmare

Introduction: Cranioplasties routinely comprise of either autologous bone graft, alloplast such as titanium or calcium phosphate based cranioplast. Here we present an unusual case combining the implementation of a novel patient specific implant (PSI) for the reconstruction of an abnormally large calvarial defect secondary to bony invasion from an extensive squamous cell carcinoma (SCC) of the scalp.

Atypical and incomplete pulmonary hypertrophic osteoarthropathy in the left distal femur: a case report

BackgroundPulmonary hypertrophic osteoarthropathy (PHO) is a rare paraneoplastic syndrome that mainly occurs in patients with lung cancer. Most symptoms occur symmetrically, and unilateral symptoms without clubbing are infrequent. This report presents the case of a rare atypical symptom that was highly suspected of being PHO.Case presentationA 77-year-old woman with swelling and severe pain in the left femur for 2 months was referred to our hospital. Radiography revealed a remarkably osteogenic thickening and sclerotic lesion in her distal femur. Preliminary diagnoses of malignant bone tumor and hematological tumor were made based on laboratory test results, radiological examination, and clinical manifestation. A needle biopsy was performed, which ruled out the diagnosis of malignant bone tumors. A low-grade bone tumor was still suspected. After that, en bloc resection was performed, followed by replacement of the femur with a mega-prosthesis. Pathological analysis revealed no malignant tumor cells, and immunohistochemical staining for CDK4 and MDM2 yielded negative results. Meanwhile, pulmonary large cell carcinoma was identified on biopsy. Based on published studies, a diagnosis of atypical PHO was made according to clinical and imaging manifestations.ConclusionsThis is an infrequent case of PHO with unilateral symptoms in the left femur. When clinical manifestations and radiological findings are inconsistent with the pathological results, the possibility of benign lesions with malignant clinical manifestations or imaging features should be carefully considered.

Lectin Histochemical Detection of N-Acetyl Glucosamine and L-Fucose Containing glycoconjugates in Lung Carcinoma

Background: Lung cancer has the highest frequency among cancers worldwide. It is the leading cause of cancer-induced death in industrialized countries. Abnormal glycosylation of cell surface and extracellular matrix glycoconjugates are among the most critical issues in neoplasia. Objectives: This present study aimed to detect N – acetyl glucosamine (GlcNac) and L- fucose (L-fuc) containing glycoconjugates in lung cancer. Methods: In this cross-sectional study, we selected paraffin blocks belonging to 25 patients with lung cancer from their pathology files at the Ali-Ebne Abitaleb Hospital, Zahedan, Iran. Six µm sections were obtained from the blocks and stained with Hematoxylin-Eosin (H-E) and lectin histochemistry (UEA and SBA lectins). Alcian Blue pH 2.5 was used as a counterstain; lectins were diluted up to 10µg/ml, and DAB was used as a chromogen. Histochemical grading was conducted blindly according to staining intensity to lectins (0-3). The data was collected and analyzed by the Mann-Whitney U test, using SPSS. Results: Statistical analysis showed that there was a significant difference between inflammatory mucosa of the bronchial tree and all types of lung cancer (i.e., adenocarcinoma and squamous cell carcinoma, as well as small and large cell lung carcinoma) according to staining intensity to SBA and UEA lectins (P < 0.001). Our results showed that there were many different patterns of reaction to SBA and UEA lectins between all types of lung cancer cells and epithelial cells of the bronchial tree. Conclusions: Staining intensity and pattern of reaction to lectins were different between all types of lung cancer cells and epithelial mucosa.

Impact of the preoperative body mass index on the postoperative outcomes in patients with completely resected non-small cell lung cancer: A retrospective analysis of 16,503 cases in a Japanese Lung Cancer Registry Study

ObjectivesThe aim of this study was to evaluate the impact of the preoperative body mass index (BMI) on the postoperative outcomes in patients with completely resected non-small cell lung cancer (NSCLC). Materials and methodsThe data of patients with NSCLC in whom R0 resection was achieved were extracted from the database of NSCLC samples accumulated by the Japanese Joint Committee of Lung Cancer Registry in the year 2010, and the surgical outcomes including postoperative morbidity, mortality and the prognosis, were evaluated. ResultsAmong 18,978 registered lung cancer cases, 16,509 patients (9996 men and 6513 women) were extracted. The median of age was 69 years old, and the histologic types included adenocarcinoma (n = 12,029), squamous cell carcinoma (n = 3286), large-cell carcinoma (n = 488) and others. The patients were divided into three groups according to their BMI: normal (BMI 18.5 to <25), underweight (BMI < 18.5) and overweight (BMI ≥ 25). Multivariate logistic regression analyses of factors associated with postoperative morbidity and mortality showed no significant differences among the three groups. In comparison to the normal group, the overall survival (OS) of the underweight group was significantly worse (p < 0.001) while that of the overweight group was marginally better (p = 0.075). A multivariate analysis of factors associated with OS showed that in addition to the age, sex and clinical stage, the preoperative BMI (underweight group vs. normal group: hazard ratio [HR] 1.417 [95% confidence interval {CI}: 1.278–1.572, p < 0.001], overweight group vs. normal group: HR 0.883 [95% CI: 0.806−0.967, p = 0.007]) was an independent prognostic factor. A multivariate analysis for the disease-free survival (DFS) also showed the preoperative BMI to be an independent significant prognostic factor. ConclusionsThe preoperative BMI is an independent prognostic factor in patients with completely resected NSCLC. A low preoperative BMI was associated with significantly poor survival in Japan.

Synthesis, Spectroscopic Characterization, Structural Studies, and In Vitro Antitumor Activities of Pyridine-3-carbaldehyde Thiosemicarbazone Derivatives

Eight new thiosemicarbazone derivatives, 6-(1-trifluoroethoxy)pyridine-3-carbaldehyde thiosemicarbazone (1), 6-(4′-fluorophenyl)pyridine-3-carbaldehyde thiosemicarbazone (2), 5-chloro-pyridine-3-carbaldehyde thiosemicarbazone (3), 2-chloro-5-bromo-pyridine-3-carbaldehyde thiosemicarbazone (4), 6-(3′,4′-dimethoxyphenyl)pyridine-3-carbaldehyde thiosemicarbazone (5), 2-chloro-5-fluor-pyridine-3-carbaldehyde thiosemicarbazone, (6), 5-iodo-pyridine-3-carbaldehyde thiosemicarbazone (7), and 6-(3′,5′-dichlorophenyl)pyridine-3-carbaldehyde thiosemicarbazone (8) were synthesized, from the reaction of the corresponding pyridine-3-carbaldehyde with thiosemicarbazide. The synthesized compounds were characterized by ESI-Mass, UV-Vis, IR, and NMR (1H, 13C, 19F) spectroscopic techniques. Molar mass values and spectroscopic data are consistent with the proposed structural formulas. The molecular structure of 7 has been also confirmed by single crystal X-ray diffraction. In the solid state 7 exists in the E conformation about the N2-N3 bond; 7 also presents the E conformation in solution, as evidenced by 1H NMR spectroscopy. The in vitro antitumor activity of the synthesized compounds was studied on six human tumor cell lines: H460 (lung large cell carcinoma), HuTu80 (duodenum adenocarcinoma), DU145 (prostate carcinoma), MCF-7 (breast adenocarcinoma), M-14 (amelanotic melanoma), and HT-29 (colon adenocarcinoma). Furthermore, toxicity studies in 3T3 normal cells were carried out for the prepared compounds. The results were expressed as IC50 and the selectivity index (SI) was calculated. Biological studies revealed that 1 (IC50 = 3.36 to 21.35 μM) displayed the highest antiproliferative activity, as compared to the other tested thiosemicarbazones (IC50 = 40.00 to &gt;582.26 μM) against different types of human tumor cell lines. 1 was found to be about twice as cytotoxic (SI = 1.82) than 5-fluorouracile (5-FU) against the M14 cell line, indicating its efficiency in inhibiting the cell growth even at low concentrations. A slightly less efficient activity was shown by 1 towards the HuTu80 and MCF7 tumor cell lines, as compared to that of 5-FU. Therefore, 1 can be considered as a promising candidate to be used as a pharmacological agent, since it presents significant activity and was found to be more innocuous than the 5-FU anticancer drug against the 3T3 mouse embryo fibroblast cells.

SURGICAL TREATMENT OF SOLITARY ADRENAL METASTASIS FROM NON-SMALL CELL LUNG CANCER

Background . Adrenal glands are the site of solitary synchronous and metachronous metastases in non-small cell lung cancer (NSCLC). The presence of solitary adrenal metastasis from lung cancer provides survival benefit; however, currently, there are no exact treatment algorithms. Objectives of the study : to assess shortand long-term treatment outcomes in patients with adrenal metastases from NSCLC. Material and methods . Treatment outcomes of patients undergoing adrenalectomy for NSCLC were analyzed. Results . From 1993 to 2014, 13 patients (11 males/2 females aged between 44 and 78, median age 58 years) with solitary adrenal metastases (adenocarcinoma (n=7), squamous cell carcinoma (n=4), large cell carcinoma (n=2); synchronous metastases – 5 cases (38.5%) and metachronous metastases – 8 cases (61.5 %), underwent adrenalectomy (one patient was given stereotactic radiation therapy for brain metastasis). Laparoscopic adrenalectomy was performed in 10 (76.9 %) cases, open adrenalectomy was performed in 3 (23.1 %) cases. The average adrenal tumor diameter was 74.6 ± 13.3 mm (25–170 mm). In the early postoperative period, two lethal outcomes were recorded. The median follow-up time after adrenalectomy was 20 months (3 to 267 months), the average follow-up time was 51.5 ± 23.5 months. The 3-year overall survival rates in patients with synchronous and metachronous metastases were 25.0 ± 2.2 % and 57.1 ± 1.9 %, respectively; however, the differences were not statistically significant (p=0.63; LogRank). The extent of surgery, morphological tumor type and status of regional lymph nodes produced no influence on the survival rate (p>0.05). Conclusion . No factors influencing survival in patients with solitary adrenal metastases from NSCLC were identified.

Adoptive transfer of zoledronate-expanded autologous Vγ9Vδ2 T-cells in patients with treatment-refractory non-small-cell lung cancer: a multicenter, open-label, single-arm, phase 2 study

BackgroundNot all non-small cell lung cancer (NSCLC) patients possess drug-targetable driver mutations, and response rates to immune checkpoint blockade therapies also remain unsatisfactory. Therefore, more effective treatments are still needed....

Atypical course of typical lung carcinoid

Carcinoids have been classified according to their embryonic origin in the past and are now categorized and classified as neuroendocrine tumors, including low malignant typical carcinoids, moderate malignant atypical carcinoids, and highly malignant large cell neuroendocrine and small cell carcinomas. A typical carcinoid is a previously used term for the current designation of a grade I neuroendocrine tumor, well differentiated, belonging to a group of rare tumors with a good prognosis with metastasis of less than 15% with a five-year survival of more than 90%, rarely producing serotonin. Even this bio-logically favorable tumor with a relatively low degree of metastasis cannot be underestimated. Case: The following section summarizes the classification of neuroendocrine tumors, their dia-gnosis and treatment, and the second section presents a specific case of a patient with multiple metastases of an original lung carcinoid (histology at the time of surgery 2012, at the time of using this older version of neuroendocrine tumors) describing its further treatment. Conclusion: In well differentiated neuroendocrine tumors, there is a significant risk of metastasis despite their radical surgery; their dispensarization is therefore necessary. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Abstract 4035: Cannabidiol inhibits the long-term survival of a variety of cancers

Abstract Cannabis has resurfaced as a natural alternative or adjunctive treatment for a variety of chronic conditions, such as anorexia in patients with the AIDS wasting syndrome and chemotherapy-related nausea and vomiting. Exogenous cannabinoids, such as Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), are found in the cannabis sativa plant. CBD has been shown to have anti-proliferative and pro-apoptotic effects in addition to preventing invasion and metastasis of various cancer cells. Such effects of CBD have been shown in certain cell lines of breast cancer, leukemia, glioma, small cell lung cancer, and colorectal cancer. Currently, the mechanism by which CBD exerts its effects are not fully understood. Here we have investigated CBD's effects on the long-term viability and mechanisms of cell death in a variety of cancer cell lines. Cancer cell lines of osteosarcoma (U2-OS), adenocarcinoma of the cervix (HeLa 1.2.11), metastatic breast cancer (MDA-MB 231), large cell lung carcinoma (H460) and malignant melanoma (A375) were plated on 12-well plates. 100% pure CBD isolated from cannabis sativa (generously provided by America's Finest CBD) was dissolved in ethanol and added directly to growth medium at various concentrations to determine the optimal dose in which the cells could no longer maintain viability. After 7-10 days, cells were stained with crystal violet. The blue dye was later extracted, quantified with a spectrometer, and dose response curves were plotted. For PARP cleavage analysis, cells were exposed to a certain concertation of CBD concentration and collected over 24-hour intervals. In addition, we have also performed RNA sequencing (RNA Seq) analysis using the melanoma cell line, A375, in an attempt to uncover the molecular mechanism of cell death induced by CBD treatment. Our long-term viability analysis demonstrate that a dose dependent response was present for each cell line exposed to CBD. We showed that CBD allows for a dose dependent killing in a variety of cancer cell lines, including large cell lung carcinoma, metastatic breast cancer, malignant melanoma, cervical carcinoma and osteosarcoma. IC50 of each cell line was determined as follows: A375 - 2.45μM, H460 - 8.47 μM, MDA-MB-231 - 8.35 μM, HeLa1.2.11 - 4.1 μM, and U2OS - 4.63 μM. The more aggressive cancer cell lines H460 and MDA-MB-231 required relatively higher dosages of CBD to kill the cells. A375, a malignant melanoma cell line, is the most sensitive cancer cell line to CBD tested so far. Apoptosis as a mechanism of cell death was confirmed with the presence of PARP cleavage in A375, H460, and MDA-MB-231 cell lines. Preliminary RNA Sequencing results suggest that heightened endoplasmic reticulum (ER) stress response in CBD treated cells is likely the cause of cell death. In summary, CBD demonstrates dose-dependent killing effects on a wide range of cancer cell lines, many of which have demonstrated a mechanism through apoptosis. Intriguingly, one of the melanoma cell lines is the most sensitive cancer cell line tested so far. Our RNA Sequencing analysis showed that CBD treatment induces a drastic increase of ER stress response, suggesting a potential mechanism of CBD induced apoptosis in cancers. In the future, we plan to develop a CBD cream and test its efficacy on preventing and/or treating skin cancers. Citation Format: Emily Seltzer, Andrea Watters, Dong Zhang. Cannabidiol inhibits the long-term survival of a variety of cancers [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4035.

Abstract 1069: Autologous γδ T cell therapy for treatment-refractory non-small-cell lung cancer: An open-label, single-arm, multicenter, phase II study

Abstract Background: Only a fraction of non-small cell lung cancer (NSCLC) patients possess targetable driver mutations, and the response rates of immune checkpoint blockades are still unsatisfactory. Therefore, the development of more effective therapies is needed for treatment-refractory NSCLC. We conducted a phase I clinical study of autologous γδ T cell therapy for NSCLC patients and reported safety and feasibility. Here, we report the result of phase II clinical trial of adoptive γδ T cell transfer therapy for treatment-refractory NSCLC patients. Methods: Patients with NSCLC who had undergone at least two regimens of standard chemotherapy for unresectable disease or who had undergone at least one treatment including chemotherapy or radiation for recurrent disease after surgery were enrolled in this open-label, single-arm, multicenter, phase II study. After preliminary testing of γδ T cell proliferative capacity, mononuclear cells of the patient collected by peripheral blood leukapheresis were cultured with zoledronic acid and IL-2. Expanded autologous γδ T cells (&amp;gt;1 × 109) were transferred intravenously every two weeks for a total of six injections. If the patient perceived some clinical benefit, the patient could continue further treatments until the disease became progressive. The primary endpoint of this study was progression-free survival (PFS), and the secondary endpoints included overall survival (OS), best objective response rate (ORR), disease control rate (DCR), and safety. The clinical efficacy of the treatment was determined if the median PFS is significantly longer than 3 months. Results: Autologous γδ T cell therapy was given for 25 patients, and 16 patients completed the 6 courses of the treatment. Among the 25 patients, 20 had adenocarcinoma, 4 squamous cell carcinoma and 1 large cell carcinoma. The median PFS was 95.0 days (95% CI 73.0-132.0 days). The median OS was 418.0 days (179.0-479.0 days). The best overall responses were 1 partial response (PR), 16 stable disease (SD) including 4 patients whose time to progression was longer than 180 days, and 8 progressive disease (PD). ORR and DCR were 4.0% (0.1-20.4%) and 68.0% (46.5-85.1%), respectively. Severe adverse events (SAE) were developed in 9 patients during the study, including pleural effusion, anorexia, cough, dyspnea, respiratory failure, pneumonitis, ascites, tumor pain, and intracranial hemorrhage. Most of them were associated with disease progression; however, a case of pneumonitis was related to γδ T cell therapy. Conclusion: Although the trial did not meet its primary efficacy endpoint, the results of this study indicate that autologous γδ T cell therapy was well tolerated and may have an acceptable disease control rate. Considering the unique mechanism of action towards tumor cells, γδ T cell therapy may be a candidate counterpart of combination therapy for treatment-refractory NSCLC. Citation Format: Kazuhiro Kakimi, Hirokazu Matsushita, Takamichi Izumi, Keita Masuzawa, Takahiro Karasaki, Shinnosuke Ikemura, Kentaro Kitano, Ichiro Kawata, Tadashi Manabe, Tomohiro Takehara, Toshiaki Ebisudani, Kazuiro Nagayama, Hiroyuki Yasuda, Masaaki Sato, Kenzo Soejima, Jun Nakajima. Autologous γδ T cell therapy for treatment-refractory non-small-cell lung cancer: An open-label, single-arm, multicenter, phase II study [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1069.

Diagnostic Value of Spectral CT Parameters in Differentiating Different Types of Lung Cancer

Background: This study proposed to quantitatively assess the value of spectral CT imaging parameters in differentiating different pathological types of lung cancer. Methods: Eighty five patients with lung cancer (66 non-mucinous adenocarcinomas, 7 Squamous cell carcinomas, 8 small cell carcinomas, 1 mucinous adenocarcinoma, 1 sarcomatoid carcinoma, 1 carcinoid, 1 large cell carcinoma) underwent CT plain scan, contrast enhanced CT scans in arterial phase (a) and venous phase (v) with spectral imaging mode on a GE Revolution Xtream CT scanner. The Spectral CT Imaging parameters: Iodine concentrations (IC) of lesion in arterial phase (ICLa) and venous phase (ICLv), Normalized IC (NICa/NICv)-normalized to the IC in the aorta, slope of the spectral HU curve (λHUa/λHUv) and monochromatic CT number (CT40keVa/CT40keVv, CT70keVa/CT70keVv) enhancement on 40 keV and 70 keV images were calculated. The One-way ANOVA or Kruskal-Wallis test was used to compare quantitative parameters among lung squamous carcinoma, small cell carcinoma and lung adenocarcinoma groups, Bonferroni method was used to correct P value for multiple comparisons. Results: Among the different pathological types of lung cancers, these quantitative parameters of spectral CT imaging CT70keVa has significant difference. The CT70keVa of lung adenocarcinoma was lower than small cell carcinoma (P = 0.048) and squamous cell carcinoma (P = 0.039), respectively. And these CT40keVa, CT70keVa/CT70keVv parameters of lung adenocarcinoma was lower than non-adenocarcinomas (P &lt; 0.05). However, there was no significant difference in spectral CT parameters between small cell lung cancer and squamous cell lung cancer, small cell lung cancer and non-small cell carcinoma (P &gt; 0.05). Conclusion: Spectral CT parameters may be of value in distinguishing different pathological types of lung cancer.

Large cell carcinoma of the lung presenting as diffuse pulmonary infiltrates with haemoptysis

AbstractDue to rapid advances in our understanding of the molecular pathogenesis of non‐small cell lung cancer (NSCLC), the 2015 World Health Organization (WHO) classification has defined large cell carcinoma (LCC) as a subtype that is lacking glandular or squamous cells, and any neuroendocrine differentiation. Accordingly, LCC is one of the rarest subtypes of NSCLC. LCC usually presents as a large peripheral tumour with prominent necrosis and its specific characteristics are not well known. Here, we report a case of LCC identified during differential diagnosis of diffuse alveolar haemorrhage in a patient with haemoptysis.

Absence of CD74 Isoform at 41kDa Prevents the Heterotypic Associations between CD74 and CD44 in Human Lung Adenocarcinoma-derived Cells

ABSTRACT Lung cancer is a leading cause of cancer-associated death in all over the globe. This study was undertaken to determine the expression and interaction of membrane-bound receptors CD74 and CD44 in human lung adenocarcinoma cells and their associated signaling was also attempted. Levels of CD74 and CD44 were studied in human lung adenocarcinoma-evolved cells A549 and H460. CD74-mediated downstream signaling was studied by the nuclear-transcription-factor NF-κB and prostaglandin E2 (PGE2) production. Flow-cytometric analysis showed that both CD74 and CD44 were perfectly expressed in A549 cells. Importantly, Western immunoblotting showed that A549 cells expressed only two isoforms of CD74 at 33 and 35 kDa but isoform at 41 kDa was absent. These results were verified in H460 cells. Confocal microscopy showed CD74 and CD44 was colocalized but heterotypic interaction between them was missing in both A549 and H460 cells. Activation of NF-κB and production of PGE2 in human lung cancer cells were comparable with other cancer cells. In conclusion, this is the first study that shows A549 and H460 cells expressed two distinctive isoforms of CD74 but isoform at 41 kDa was absent. Due to the absence of this isoform, the direct physical interaction between them CD74 and CD44 was lacking. Furthermore, the data also demonstrated that lacking of direct physical interaction between CD74 and CD44 had no effect on NF-κB activation and PGE2 production indicating that CD74-mediated downstream signaling occurs either through coreceptors or indirect interaction with CD44 in human lung cancer cells. Abbreviation: CD: cluster of differentiation; SCLC: small cell lung cancer; NSCLC: nonsmall cell lung cancer; SCC: squamous cell carcinoma; ADC: adenocarcinoma; LCC: large cell carcinoma

Vismodegib therapy for a large basal cell carcinoma on the midface with orbital involvement

Vismodegib therapy for a large basal cell carcinoma on the midface with orbital involvement

Non Small Cell Lung Cancer Classification from Histopathological Images using Feature Fusion and Deep CNN

Lung cancer is the overgrowth of cells in digestive organs. Identifying different types of lung cancer (squamous cell cancer, large cell carcinoma and adenocarcinoma) from lung histopathological images is outrageous works that shorten the chance of infected with lung cancer in the future. This research propounds an accurate diagnosis scheme using various neural network features and fusion of contourlet transform from lung histopathological image. This lesson has used several pre-train models (Alexnet, ResNet50, and VGG-16) in addition to divers scratch models while the pre-train Resnet50 model works better. The two reduction techniques (Principle Component Analysis (PCA) and Minimum Redundancy Maximum Relevance (MRMR)) have used to classify the type of lung cancer with the extraction of the most significant properties. In Convolution Neural Network (CNN) based lung cancer detection, the reduction approach PCA performs better. This proposed methodology is performed on ordinary datasets and establishes comparative better performance. The accuracy of this paper is 98.5%, sensitivity 96.50, specificity 97.00%, which is more effective than other approaches.

Cashew apple (Anacardium occidentale L.) extract from a by-product of juice processing: assessment of its toxicity, antiproliferative and antimicrobial activities.

Cashew apple extract (CAE) is a product with intense yellow color obtained from residual fibers of juice processing. Although CAE is known to be rich in carotenoids and anacardic acids, the biological activities of this potential natural food colorant remain unexplored. The present study is the first to investigate the toxicity, antiproliferative and antimicrobial activities of the lyophilized CAE (L-CAE) and its encapsulated products, using maltodextrin (M-CAE) or cashew gum (CG-CAE) as carriers. In addition to their high carotenoid content, the phenolic contents in all materials was determined using UPLC-QTOF-MSE. The acute toxicity was performed using adult zebrafish (Danio rerio); antiproliferative activity was assessed using seven different human tumor cell lines [U-251 (glioblastoma), MCF-7 (breast, adenocarcinoma), NCI-ADR/RES (multidrug-resistant ovarian adenocarcinoma), NCI-H-460 (lung, large cell carcinoma), PC-3 (prostate, adenocarcinoma), OVCAR-3 (ovarian adenocarcinoma), and HT-29 (colon, adenocarcinoma)] and an immortalized human keratinocyte (HaCaT) while the antimicrobioal activity was evaluated on Staphylococcus aureus ATCC 25923, Listeria monocytogenes ATCC 19115, Escherichia coli ATCC 25922 and Salmonella Typhimurium ATCC 51812 microorganisms. Both lyophilized and encapsulated CAE samples did not exert acute toxicity against zebrafish neither antiproliferative effect against human tumor and non-tumor cell lines. Further, L-CAE showed potential antimicrobial activity against Listeria monocytogenes, which was confirmed using electron microscopy. The current findings demonstrated that CAE is a potential source of bioactive compounds to use as an additive in the food industry.