Cell Type Adenocarcinoma Research Articles

Immunohistochemical p16 overexpression and Rb loss correlate with high-risk human papillomavirus infection in endocervical adenocarcinomas.

p16 is a sensitive surrogate marker for transcriptionally active high-risk human papillomavirus (HR-HPV) infection in endocervical adenocarcinoma (ECA); however, its specificity is not perfect. We examined p16 and Rb expressions by immunohistochemistry (IHC) and the transcriptionally active HR-HPV infection by mRNA in-situ hybridisation (ISH) with histological review in 108 ECA cases. Thirteen adenocarcinomas of endometrial or equivocal origin (six endometrioid and seven serous carcinomas) were compared as the control group. HR-HPV was detected in 83 of 108 ECA cases (77%), including five HPV-associated adenocarcinomas in situ and 78 invasive HPV-associated adenocarcinomas. All 83 HPV-positive cases showed consistent morphology, p16 positivity and partial loss pattern of Rb. Among the 25 cases of HPV-independent adenocarcinoma, four (16%) were positive for p16, and of these four cases, three of 14 (21%) were gastric type adenocarcinomas and one of 10 (10%) was a clear cell type adenocarcinoma. All 25 HPV-independent adenocarcinomas showed preserved expression of Rb irrespective of the p16 status. Similarly, all 13 cases of the control group were negative for HR-HPV with preserved expression of Rb, even though six of 13 (46%) cases were positive for p16. Compared with p16 alone, the combination of p16 overexpression and Rb partial loss pattern showed equally excellent sensitivity (each 100%) and improved specificity (100 versus 73.6%) and positive predictive values (100 versus 89.2%) in the ECA and control groups. Furthermore, HR-HPV infection correlated with better prognosis among invasive ECAs. The results suggest that the combined use of p16 and Rb IHC could be a reliable method to predict HR-HPV infection in primary ECAs and mimics. This finding may contribute to prognostic prediction and therapeutic strategy.

Abstract A019: eIF4A and PDCD4 expression in TNBC underlies sensitivity to natural product translation inhibitor

Abstract Despite recent advances in immunotherapy and adjuvant-therapy, resistance to cancer therapeutics is common and requires novel approaches. Moreover, highly aggressive triple-negative breast cancers lack effective targeted treatments. Deregulation of translation factors is associated with the increased proliferation of TNBC cells, heightened CSC activity, and poor patient outcomes. Thus targeting translation regulatory factors upregulated in TNBC is a promising approach to developing novel treatments. Pateamine A (PatA), a natural marine macrodiolide product, inhibits RNA cap-dependent translation by binding and sequestering the eukaryotic translation initiation factor eIF4A. eIF4A promotes the translation of polypurine-rich mRNA sequences, which are enriched within breast cancer oncogenes. Here we report the anticancer efficacy of novel PatA analogs we have synthesized against breast cancer cell lines. The PatA analogs exhibited selective cytotoxicity to breast and colorectal cancers compared to non-cancerous cells measured by Cell Titer-Blue viability studies. Novel analogs show greater antiproliferative potency against models of triple-negative than against human mammary epithelial cells (HMLE). To further elucidate eIF4A as a molecular target, we conducted analyses of patient tissue samples in the Cancer Genome Atlas (TCGA). Our analyses reveal the overexpression of eIF4A in tumor tissues compared to normal tissues and gene correlation studies reveal the upregulation of key co-expressed tumor drivers including beta-catenin, fibronectin, and epithelial-to-mesenchymal transition (EMT) markers such as SNAIL and SLUG. Further analyses show a downregulation of tumor suppressor protein PDCD4, an endogenous inhibitor of eIF4A, in cancer tissues. We have generated eIF4A shRNA knockdown and PDCD4 shRNA knockdown cell lines to uncover the eIF4A-PDCD4 regulatory axis across breast adenocarcinoma and colorectal adenocarcinoma cell types. We show that the loss of eIF4A attenuates the mesenchymal and stem-like phenotype of breast cancer stem cells revealed by phenotypic assays. Our results suggest that targeting translation initiator eIF4A is an effective approach against highly proliferative and metastatic breast cancer types. The presented findings underscore the potential of eIF4A as a promising molecular target and supports translational control as a viable approach against aggressive cancers. Citation Format: Alagu Subramanian, Haoran Xue, Kenneth G Hull, Daniel Romo, Joseph Taube. eIF4A and PDCD4 expression in TNBC underlies sensitivity to natural product translation inhibitor [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A019.

The prognosis of clinical stage IIIa non-small cell lung cancer in Taiwan.

Lung cancer is the leading cause of cancer death. The treatment of stage IIIa remained the most controversial of all stages of non-small cell lung cancer (NSCLC). We reported on the heterogenicity and current treatment strategies of stage IIIa NSCLC in Taiwan. This study is a retrospective analysis using data from the Taiwan Society of Cancer Registry between January 2010 and December 2018. 4232 patients with stage IIIa NSCLC were included. Based on cell type, the best 5-year OS (40.40%) occurred among adenocarcinoma victims. The heterogenicity of T1N2 had the best 5-year OS (47.62%), followed by T4N0 (39.82%), and the others. Patients who underwent operations had better 5-year OS (over 50%) than those who did not (less than 30%). Segmentectomy (75.28%) and lobectomy (54.06%) showed better 5-year OS than other surgical methods (less than 50%). In multivariable analysis, young age, female, lower Charlson Comorbidity Index score, adenocarcinoma cell type, well differentiated, T1N2/T4N0 heterogenicity, treatment with operation, and segmentectomy/lobectomy/bilobectomy were significant factors. In conclusions, the heterogenicity of T1N2 had the best outcomes followed by T4N0. Patients received surgical treatment revealed much better outcomes than those did not. As always, multimodal therapies with individualized treatment tend to provide better survival outcomes.

Association between exposures to radon and γ-ray radiation and histologic type of lung cancer in Eldorado uranium mining and milling workers from Canada.

BackgroundThe authors assessed the association between radon decay products (RDP) exposure and histologic types of incident lung cancer in a cohort of 16,752 (91.6% male) Eldorado uranium workers who were first employed from 1932 to 1980 and were followed through 1969–1999.MethodsSubstantially revised identifying information and RDP exposures were obtained on workers from the Port Radium and Beaverlodge uranium mines and from the Port Hope radium and uranium refinery and processing facility in Canada. Poisson regression was conducted using the National Research Council's Biological Effects of Ionizing Radiation (BEIR) VI–type models to estimate the risks of lung cancer by histologic type from RDP exposures and γ‐ray doses.ResultsLung cancer incidence was significantly higher in workers compared with the general Canadian male population. Radiation risks of lung cancer for all histologic types (n = 594; 34% squamous cell, 16% small cell, 17% adenocarcinoma) increased with increasing RDP exposure, with no indication of curvature in the dose response (excess relative risk per 100 working level months = 0.61; 95% confidence interval, 0.39–0.91). Radiation risks did not differ by histologic type (p = .144). The best‐fitting BEIR VI–type model included adjustments for the significant modifying effects of time since exposure, exposure rate, and attained age. The addition of γ‐ray doses to the model with RDP exposures improved the model fit, but the risk estimates remained unchanged.ConclusionsThe first analysis of radiation risks of lung cancer histologic types in the Eldorado cohort supported the use of BEIR VI–type models to predict the future risk of histologic types of lung cancer from past and current RDP exposures.Lay summary Lung cancer survival depends strongly on the cell type of lung cancer.The best survival rates are for patients who have the adenocarcinoma type.This study included 16,752 Eldorado uranium workers who were exposed to radon and γ‐ray radiation during 1932–1980, were alive in 1969, and were followed for the development of new lung cancer during 1969–1999.One third of all lung cancers were of the squamous cell type, whereas the adenocarcinoma and small cell types accounted for less than 20% each.Radiation risks of lung cancer among men increased significantly with increasing radon exposure for all cell types, with the highest risks estimated for small cell and squamous cell lung cancers.

Balstilimab and other immunotherapy for recurrent and metastatic cervical cancer.

Recurrent and metastatic cervical cancer is generally treated by cisplatin, paclitaxel, and bevacizumab with limited benefit this constituting an unmet need. Immune checkpoint inhibitors, namely the inhibitors of programmed death 1 and programmed death ligand 1 have been proved to be efficacious in the treatment of patients with advanced cervical cancer. Recently, a PD-1 inhibitor, pembrolizumab was approvedfor such cancer. However, there is much scope of improvement of current outcome. Dual blockade of cytotoxic T lymphocyte-associated protein 4 and PD-1 is an attractive therapeutic approach. It is used in other cancers and is currently proposed for cancer cervix also. Search is on for single or combined regimen showing efficacy in multiple pathological conditions of cancer cervix irrespective presence of PD-L1 in malignant tissue. An effort to meet such unmet need has culminated in inventing new immune checkpoint inhibitors namely PD-1 inhibitor, AGEN2034 (Balstilimab) and CTLA-4 inhibitor, AGEN1884 (Zalifrelimab).They have shown meaningful and durable activity as single-agent therapy in previously treated patients with persistent R/M CC in a large phase II trial (NCT03104699) in PD-L1 + and PD-L1- tumour. Responses were found both in squamous cell carcinoma & adenocarcinoma cell types. Balstilimab plus zalifrelimab combination (NCT03495882) produced improved clinical benefit over monotherapy as evidenced by higher relative response rates and longer response duration, as well as a manageable safety profile. Interesting development of this combination and other immunotherapies in R/M CC are discussed in this ensuing review.

The Differences in Urokinase Plasminogen Activator System in Lung Cancer Patients Before and After Chemotherapy

Background: Lung cancer is still the leading cause of death for malignancies worldwide. Urokinase plasminogen activator (uPA), its soluble receptor (suPAR), and its inhibitor (PAI-1) play an important role in tumor invasion and metastasis. This study aimed to evaluate the differences in the urokinase plasminogen activator system (uPA, suPAR, and PAI-1) in lung cancer patients before and after chemotherapy.Methods: This research was an observational analytical study with a cross-sectional design. The subjects were 30, consisting of 17 lung cancer patients before chemotherapy and 13 lung cancer patients after chemotherapy for 4 or 6 cycles. The levels of serum uPA, suPAR, and PAI-1 were measured by enzyme-linked immunosorbent assay (ELISA). Results: In lung cancer patients before chemotherapy, there were no significant (p>0.05) differences in levels of serum uPA, suPAR, and PAI-1 between patients with stage III and IV. The highest serum uPA and suPAR levels were found in adenocarcinoma cell types and the highest serum PAI-1 level in adenoepidermoid cell types. After chemotherapy, serum suPAR and PAI-1 were significantly (p < 0.05) decreased in lung cancer patients. However, there were no significant (p>0.05) differences in the levels of serum uPA, suPAR, and PAI-1 between patients with chemotherapy responses for stable and progressive diseases. Conclusion: This study revealed that suPAR and PAI-1 levels were decreased in lung cancer patients who had received chemotherapy. This can occur due to decreased tumor cells activity.

The Prevalence of Adenocarcinoma in Non-small Cell Lung Cancer Patients at Chulabhorn Hospital

Objective: To study the prevalence of the adenocarcinoma cell type in non-small cell lung cancer cases at Chulabhorn Hospital and examine the correlation between histology type and survival of patients. Materials and Methods: We examined the medical records of non-small cell lung cancer cases treated in Chulabhorn Hospital from January 2009 to December 2011. Baseline demographic data and cancer treatment information were obtained for survival analyses. Results: Among 62 cases of non-small cell lung cancer, 67.7% were the adenocarcinoma subtype. The median survival of non-small cell lung cancer cases was 11 months (95% CI; 9.0 to 18.0), 12 months in adenocarcinoma group and 7.4 months in squamous cell carcinoma group. There was statistically significant differences of survival among different histology(p=0.006). There was a slightly higher incidence of adenocarcinoma in the non-smoker group compared with the smoker group, 67.7% vs. 64.7%, respectively. Smoking status was significantly associated with histology subtype (p=0.034). Conclusion: The adenocarcinoma subtype was found in approximately two-thirds of non-small cell lung cancer cases at Chulabhorn hospital. The median survival of patients with the adenocarcinoma subtype was longer than patients with the squamous cell carcinoma subtype with statistically significant. Keywords: Adenocarcinoma of lung, Non small cell lung cancer

Lipofection of Single Guide RNA Targeting MMP8 Decreases Proliferation and Migration in Lung Adenocarcinoma Cells.

Background and Objectives: Matrix metalloproteinases (MMP) have been implicated as major determinants of tumour growth and metastasis, which are considered two of the main hallmarks of cancer. The interaction of MMP8 and other signalling molecules within and adjacent tumoral tissues, including immune cells, are rather elusive, particularly of adenocarcinoma cell type. In this study, we aimed to investigate the role of MMP8 in non-small cell lung cancer proliferation and invasiveness potential. Materials and Methods: We individually lipofected with two different single guide RNA (sgRNAs) that specifically targeted on MMP8, with CRISPR-Cas 9 protein into the cells. Results: Our results clearly indicated that the lipofection of these complexes could lead to reduced ability of A549 cells to survive and proliferate to form colonies. In addition, when compared to non-transfected cells, the experimental cell groups receiving sgRNAs demonstrated relatively decreased migration rate, hence, wider wound gaps in scratch assay. The quantitative real time-polymerase chain reaction (qRT-PCR) demonstrated significant reduction in the MAP-K, survivin and PI3-K gene expression. MMP8 might have protective roles over tumour growth and spread in our body. Conclusions: The delivery of sgRNAs targeting on the MMP8 gene could induce tumour cell death and arrest cell migratory activity.

Bronchogenic carcinoma: Correlation of CT findings with the surgical and histopathological findings

CT and HRCT how largely replaced radiological procedures such has bronchography and pulmonary angiography for evolution of parenchyma lung diseases. HRCT has enabled the delineation of lung parenchyma down to the level of secondary pulmonary lobule (Mayo R et al., 1987). Further advancement in CT Technologies by spiral CT and ultra fast CT have still consolidated the role of CT in evolution thoracic diseases. Spiral CT facilitate generation of 3D images of lung that or not degraded by respiratory motion and is much faster at acquisition time ensuring evaluation of lung during maximum vascular enhancements. In this study CT evaluation of 50 patients with either proven or strongly suspected bronchogenic carcicnoma based on chest radiographs, bronchoscopy, cytology of bronchial washings or pleural fluid, FNAC or clinical examination was done. The most common cell type in bronchogenic carcinoma was squamous cell carcinoma in 33 patient (66%) followed by adenocarcinoma Majority of the adenocarcinoma cell type are presenting as central masses than peripheral (18% v/s 6%).

Characteristic gynaecology-oncology patients from Obstetrics and Gynaecology Outpatient Clinic Mangusada Regional Hospital Badung reffered to Sanglah Hospital from 1st January 2016 - 31st December 2018

Background: Every year, there is an increase in malignancy cases in the world. In women, malignancy is the second most cause of death. Gynecologic malignancy can be found in all women reproductive tract, including cervix, ovary, uterus, vagina and vulva. Most women death from gynecologic malignancy occurred in developing countries, and this is due to lack of access for early detection and treatment. The study aims to report characteristic of patients referred from Obstetrics and Gynaecology Outpatient Clinic Mangusada Hospital, Badung from January 2016 – December 2018.Results: Total referred case were 451 gynaecology-oncology patients in obstetrics and gynaecology outpatient clinic Mangusada Hospital, Badung-Indonesia. Top three most referred case were cervical cancer, ovarian cyst with malignancy suspected and ovarian cancer. For Cervical cancer, most of the patients are in group age 41-50 years old (40,3%), in-stadium III (59,2%) and squamous cell type (71,7%). For ovarian cancer, most of the patients are in group age 41-50 years old (45,1%), in-stadium III (59,2%), and epithelial type cell (87,3%). For endometrial cancer, most of the patients are in group age 51-60 years old (53,9%), in-stadium III (46,1%) and adenocarcinoma cell type (100%).Conclusion: The most common gynaecological referral cases are cervical cancer, suspicious malignant ovarian cysts, and ovarian cancer. All gynaecological cases referred to are suspected or diagnosed as gynaecological malignancies and require the handling of a gynaecology-oncology division and integrated oncology services.

Serum MiRNA as Predictive and Prognosis Biomarker in Advanced Stage Non-small Cell Lung Cancer in Indonesia

Background and objectiveLung cancer is the most common cause of death in men in the world and in Indonesia where non-small cell carcinoma lung cancer (NSCLC) constitutes 85% of all lung cancer cases. The high mortality rate is due to a poor prognosis and is often diagnosed as having advanced stages. If it is known at the initial stage, the prognosis of lung cancer will be better. Prognosis can be predicted with a marker of prognostic biology, one of which is micro RNA (miRNA). This study aims to prove that serum miRNA can be predictive biological marker and prognosis in NSCLC patients in Indonesia.MethodsThis study was cohort retrospective among 52 subjects in "Dharmais" Hospital National Cancer Center. Sample was obtained from patients' serum. MiR-34, miR-148, miR-155 and miR-222 serum are measured through Real-Time PCR (qPCR). Data were analyzed and interpreted with descriptive analysis, bivariate analysis (Mann Whitney-U for two type of variables or Kruskal-Wallis for more than two type of variables. Kaplan-Meier analysis was used to know association between characteristic which are sociodemographic, performance status, clinico-pathology, and survival rate in miRNA expression.ResultsFrom this study, miRNA expression: miR-34 (46.15%), miR-148 (23.08%), miR-155 (40.38%) and miR-222 (32.69%). Performance status score was statistically significant correlation with miR-148 (P=0.049) and miR-222 (P=0.018). High miR-34 is associated with multiple M1b metastatic type (P=0.020), cancer cell type (adenocarcinoma, P=0.009) and adenocarcinoma epidermal growth factor receptor (EGFR) mutation (negative, P=0.031). There was a significant correlation between the high miR-222 as a poor prognosis in advanced stage NSCLC with M1b metastasis (Median Survival/MS: 27 d, P=0.049) and positive EGFR mutations (MS: 74 d, P=0.049) and correlation of miR-155 with adenocarcinoma (MS: 69 d, P=0.034) and positive EGFR gene mutations (MS: 58 d, P=0.023).ConclusionHigh miR-34 expression in advanced stage NSCLC is the predictive factor for multiple metastatic, adenocarcinoma cell type and adenocarcinoma negative EGFR mutation. High expression of miR-155 and miR-222 are poor prognoses, especially high miR-222 found in metastasis M1b and positive EGFR mutation and miR-155 found in adenocarcinoma and positive EGFR gene mutations. Further studies regarding correlation between miRNA and survival rate are needed.

Proteomic and ultrastructural analysis of Clara cell and type II alveolar epithelial cell-type lung cancer cells.

BackgroundCurrently, the identification of Clara cell and type II alveolar epithelial cell-type cancer cells requires electron microscopy, which is a time-consuming and expensive process involving a complicated tissue sampling procedure. The aim of this study was to identify unique biomarkers for Clara cell and type II alveolar epithelial cell-type lung cancer cells, respectively, with proteomic profiling.MethodsSix human lung adenocarcinoma cell lines (A549, NCI-H358, NCI-H1650, HCC827, NCI-H1395, and NCI-H1975) were investigated for their ultrastructural characteristics. The differentially expressed proteins (DEPs) were screened between NCI-H358 cells (Clara cell type) and A549 cells (type II alveolar epithelial cell type) using two-dimensional difference gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS/MS), and then they were validated by western blot. The protein expression levels of endoplasmic reticulum oxidoreductin 1-α (ERO1L), Clara cell 10-kD protein (CC10), and surfactant protein C (SP-C) were also determined in the six cell lines assayed.ResultsNCI-H358 cells featured Clara cell differentiation; A549, NCI-H1975, and HCC827 cells had characteristics of type II alveolar epithelial cells; and NCI-H1395 and NCI-H1650 cells had no differentiation characteristics of any lung adenocarcinoma cell type. Five DEPs including ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL1), cytokeratin 19 (CK19), cytokeratin 8 (CK8), ERO1L, and peroxiredoxin 2 (PRDX2) between NCI-H358 and A549 cells were identified for further validation; however, none of them showed suitability as an effective biomarker. Similarly, CC10 and SP-C were not appropriate biomarkers.ConclusionsCytological subtypes of NCI-H1975 and HCC827 cells were identified, but no promising biomarker was discovered in the present study.

Adenocarcinoma de pulmón pobremente indiferenciado. A propósito de un caso

El cáncer es una de las principales causas de muerte en el mundo. Es la neoplasia más frecuente y con mayor mortalidad en ambos sexos en los países desarrollados. Su pronóstico global es malo con una supervivencia total a los 5 años del 15%. Los factores de riesgo para el CP son diversos, pero destacan el tabaquismo, tanto activo como pasivo; exposición a radiación por gas radón; dieta; exposición a compuestos químicos como asbestos, arsénico, cloruro de vinilo, cromato de níquel, clorometilo de éter, entre muchas otras sustancias más. El CP se considera como enfermedad centinela del tabaquismo por las siguientes razones: 1. Fumar tabaco es el factor de riesgo presente en 90% de los pacientes con CP. 2. El riesgo de enfermar o morir por CP en fumadores aumenta drásticamente después de los 40 años de edad. 3. Las tasas de mortalidad por CP aumentan después de los 40 años de edad, en relación directa con el consumo de tabaco. 4. Después de 10 años de abstinencia, el riesgo relativo de desarrollar CP se reduce 50% en comparación con la persistencia en el hábito. El carcinoma no de células pequeñas de pulmón (CNCP) supone el 80-85% de los CP. Incluye fundamentalmente, los siguientes tipos histológicos: epidermoide, adenocarcinoma y de células grandes. A su presentación sólo el 25% son estadios localizados, y un 35% son estadios localmente avanzados (estadio III o IV). Aproximadamente el 80% de los pacientes con CNCP presentan enfermedad metastásica en alguna de sus fases evolutivas: 30-40% al diagnóstico, 50% por recidiva de los estadios I-II y 80% por progresión o recaída de los estadios III, y su supervivencia es muy pobre. El carcinoma de células pequeñas de pulmón (CCP) constituye aproximadamente el 15-20% de las neoplasias pulmonares. Aproximadamente el 60- 70% de los pacientes tienen enfermedad diseminada en el momento del diagnóstico.

Development of an inducible CRISPR/Cas9 system for temporally‐modulated gene editing

Despite its prolific track record of research into primary tumor dynamics, the field of cancer biology has yet to develop a reliable methodology for interrogating the genetic profiles of recurrent tumors. CRISPR/Cas9 gene editing has proven to be foundational for recent advancements in oncogenetic screening, due in part to its high degree of specificity in achieving on‐target gene knockout while minimizing off‐target effects. The primary limitation to its application in screening pro‐recurrence factors in cancer, however, is the constitutive nature of canonical Cas9 activity, which may not be remotely regulated after the point of Cas9 translation. To address this problem, we cultivated and transduced populations of a resected invasive mammary adenocarcinoma cell type with a selection of four recombinant Cas9 transgenes and characterized the relative inducibility of each system. These Cas9's are fused to peptides whose tertiary structure renders the endonuclease inactive, restoring catalytic activity only in the presence of a fusion‐specific ligand. Populations of EGFP‐expressing adenocarcinoma cells were transduced with a modified estrogen receptor‐Cas9 fusion (ERT2‐Cas9) and assayed for target knockout efficiency upon addition of small guide GFP (sgGFP) and a Cas9‐enabling estrogen analog. After three days exposure to the analogue, flow cytometry revealed GFP expression to be markedly reduced in cells expressing ERT2‐Cas9 and minimal change in those not exposed. Once the timing and treatment of this model are refined, ERT2‐Cas9‐expressing adenocarcinoma cells will be orthotopically‐injected into mice for an in vivo screening assay. By equipping neoplastic cells with the inducible‐Cas9 machinery before the point of tumor outgrowth, it becomes possible to systematically screen pro‐survival factors at late time points in cancer progression without drastically disturbing the microenvironment of the tumor.Support or Funding InformationThis work was supported by ah ASPET summer research award in partnership with SURPH at Duke University.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

AFM study: Cell cycle and probe geometry influences nanomechanical characterization of Panc1 cells

Atomic force microscope (AFM) is emerging as an immensely promising tool to study the cellular morphology with a nanometer scale resolution and to analyze nanomechanical properties (NPs) at various physiological conditions. Advancement of AFM technology enables studying living cells and differentiating cancer cell from normal cells based on topography and NPs. Though the trend overlaps from different literature; numerical values of nanomechanical readouts depict variations over a wide range. These anomalies are associated with the experimental setup under study. In this manuscript, we have identified heterogeneity in cell culture system in addition to the selection of AFM probe with specific tip geometry as the major contributors to the above mentioned anomalies. To test our hypothesis, we have used Panc1 cells, which is a pancreatic ductal adenocarcinoma cell type. Our results suggest that the cellular morphology, membrane roughness and NPs calculated from AFM study are distinctly influenced by cell cycle. Furthermore, we found that the NPs readout is also significantly associated with AFM tip geometries. The cells were found to be softer in their early resting phase when indented with pyramidal probe and became increasingly stiffer as they progressed through the cell cycles. On the contrary, when indented with the spherical probe, cells in G0/G1 phase were observed to be the stiffest. Such an exhaustive study of the role of cell cycle in influencing the NPs in Panc1 cell line along with the impact of tip geometry on NPs is the first of its kind, to the best of our knowledge.

Association of Cancer Cell Type and Extracellular Vesicles With Coagulopathy in Patients With Lung Cancer and Stroke.

Coagulopathy is an important cause of stroke in cancer patients. However, underlying mechanisms and clinical factors related to coagulopathy remain unclear. We hypothesized that certain characteristics of cancer affect coagulopathy in patients with lung cancer and ischemic stroke. Consecutive patients with active lung cancer and acute ischemic stroke were prospectively studied. Volume and pattern of acute brain infarcts and plasma levels of circulating tumor extracellular vesicles (EVs) were measured using flow cytometry. In vitro experiments investigated the pathophysiological mechanisms underlying cancer-associated coagulopathy. Of 114 patients, 95 (83.3%) had an adenocarcinoma cell type and 95 (83.3%) had distant metastasis. Acute brain infarct volumes were larger and circulating EV levels were higher in patients with an adenocarcinoma cell type than in those with other cell types. The presence of metastasis was not associated with infarct volume or circulating EV levels. Coagulation assays demonstrated dose-dependent shorter clotting times after treatment with EVs from adenocarcinoma cell lines than with the use of EVs from squamous cell carcinoma. These findings were confirmed by coagulation assays using circulating EVs from patients with adenocarcinoma and stroke and from those with conventional stroke mechanisms. Our findings indicate that cancer cell type is associated with circulating EV levels and coagulopathy in patients with lung cancer and stroke.

Metastatic colonic and gastric polyps from breast cancer resembling hyperplastic polyps

Breast cancer metastasis to the gastrointestinal tract is relatively rare and is generally found when patients complain of symptoms such as gastrointestinal obstruction. Herein, we report a case with metastatic colonic and gastric lesions from breast cancer, with the formation of mucosal polyps which resembled typical hyperplastic polyps.A 47-year-old woman underwent curable surgery for breast cancer and received standard systemic treatments. Her primary tumor was composed of a mix of invasive lobular and ductal carcinomas. During adjuvant endocrine therapy, she developed multiple colonic metastases, identified by colonoscopy performed as part of a general health check-up. She had no symptoms. Small elevated sessile polyps in the transverse colon and rectum showed histological features of signet-ring cell type adenocarcinoma, similar to the invasive lobular component of the primary breast cancer. During treatments for recurrent disease, she also developed multiple gastric metastases, with the same endoscopic and pathological features as the colonic lesions. Her treatment regimen was switched to oral chemotherapy, and she has since maintained stable disease for nearly 3 years. Multiple bone metastases eventually developed, and she was again switched to another systemic treatment but, to date, has remained free of symptoms.We emphasize that the endoscopic findings of the metastatic lesions in the colon and stomach in this case highly resembled hyperplastic polyps. Since biopsy is not always performed for hyperplastic polyps in the gastrointestinal tract, we believe that this case report may encourage endoscopists to offer biopsies to the patient who has a history of breast cancer.

Post-recurrence survival analysis of stage I non-small-cell lung cancer.

Background The aim of this retrospective study was to review recurrence patterns of stage I non-small-cell lung cancer and identify prognostic factors for post-recurrence survival. Methods Among 940 patients with pathological stage I non-small-cell lung cancer who underwent curative resection, 261 experienced a recurrence; of these, 188 had adenocarcinoma and 62 had squamous cell carcinoma. Oligo-recurrence was defined as 1-3 recurrent lesions restricted to a single organ. Potentially curative local treatment included surgery, stereotactic radiotherapy, and photodynamic therapy. Results The median follow-up duration was 65 months (range 4-186 months). The most common site of recurrence was the lung in 145 patients, followed by mediastinal lymph nodes in 49, pleura in 30, and brain in 27. Local treatment for recurrent tumors included surgery in 59 patients, stereotactic radiotherapy in 46, photodynamic therapy in 2, and other radiotherapy in 41. Seventy-eight patients received chemotherapy only, and 35 received conservative treatment. Among 125 patients who were evaluated for an epidermal growth factor receptor gene mutation, 31 were treated with epidermal growth factor receptor-tyrosine kinase inhibitor. The 3- and 5-year post-recurrence survival rates were 49.1% and 33.8%, respectively. Age at recurrence, adenocarcinoma cell type, disease-free interval, epidermal growth factor receptor-tyrosine kinase inhibitor treatment, and potentially curative local treatment were independent prognostic factors for survival in multivariate analysis. Conclusions Local treatment for recurrence should be considered in selected candidates, and use of epidermal growth factor receptor-tyrosine kinase inhibitor I is reasonable if an epidermal growth factor receptor mutation is detected.

Severe Cushing's syndrome due to small cell prostate carcinoma: a case and review of literature.

Cushing’s syndrome (CS) due to ectopic adrenocorticotrophic hormone (ACTH) is associated with a variety of tumours most of which arise in the thorax or abdomen. Prostate carcinoma is a rare but important cause of rapidly progressive CS. To report a case of severe CS due to ACTH production from prostate neuroendocrine carcinoma and summarise previous published cases. A 71-year-old male presented with profound hypokalaemia, oedema and new onset hypertension. The patient reported two weeks of weight gain, muscle weakness, labile mood and insomnia. CS due to ectopic ACTH production was confirmed with failure to suppress cortisol levels following low- and high-dose dexamethasone suppression tests in the presence of a markedly elevated ACTH and a normal pituitary MRI. Computed tomography demonstrated an enlarged prostate with features of malignancy, confirmed by MRI. Subsequent prostatic biopsy confirmed neuroendocrine carcinoma of small cell type and conventional adenocarcinoma of the prostate. Adrenal steroidogenesis blockade was commenced using ketoconazole and metyrapone. Complete biochemical control of CS and evidence of disease regression on imaging occurred after four cycles of chemotherapy with carboplatin and etoposide. By the sixth cycle, the patient demonstrated radiological progression followed by recurrence of CS and died nine months after initial presentation. Prostate neuroendocrine carcinoma is a rare cause of CS that can be rapidly fatal, and early aggressive treatment of the CS is important. In CS where the cause of EAS is unable to be identified, a pelvic source should be considered and imaging of the pelvis carefully reviewed.

Cancer of the esophagus and esophagogastric junction-Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual.

Answer questions and earn CME/CNE New to the eighth edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual for epithelial cancers of the esophagus and esophagogastric junction are separate, temporally related cancer classifications: 1) before treatment decision (clinical); 2) after esophagectomy alone (pathologic); and 3) after preresection therapy followed by esophagectomy (postneoadjuvant pathologic). The addition of clinical and postneoadjuvant pathologic stage groupings was driven by a lack of correspondence of survival, and thus prognosis, between both clinical and postneoadjuvant pathologic cancer categories (facts about the cancer) and pathologic categories. This was revealed by a machine-learning analysis of 6-continent data from the Worldwide Esophageal Cancer Collaboration, with consensus of the AJCC Upper GI Expert Panel. Survival is markedly affected by histopathologic cell type (squamous cell carcinoma and adenocarcinoma) in clinically and pathologically staged patients, requiring separate stage grouping for each cell type. However, postneoadjuvant pathologic stage groups are identical. For the future, more refined and granular data are needed. This requires: 1) more accurate clinical staging; 2) innovative solutions to pathologic staging challenges in endoscopically resected cancers; 3) integration of genomics into staging; and 4) precision cancer care with targeted therapy. It is the responsibility of the oncology team to accurately determine and record registry data, which requires eliminating both common errors and those related to incompleteness and inconsistency. Despite the new complexity of eighth edition staging of cancers of the esophagus and esophagogastric junction, these key concepts and new directions will facilitate precision cancer care. CA Cancer J Clin 2017;67:304-317. © 2017 American Cancer Society.