scholarly journals Serum Levels of Kisspeptin Are Elevated in Patients with Pancreatic Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Sven H. Loosen ◽  
Mark Luedde ◽  
Georg Lurje ◽  
Martina Spehlmann ◽  
Pia Paffenholz ◽  
...  
Keyword(s):  
Performance Status ◽  
Treatment Options ◽  
Tumor Resection ◽  
Serum Levels ◽  
Ecog Performance Status ◽  
Related Factors ◽  
Suitable Treatment ◽  
Novel Biomarkers ◽  
Selection Of

Pancreatic adenocarcinoma (PDAC) still represents a devastating disease associated with a very limited survival. Novel biomarkers allowing an early diagnosis as well as an optimal selection of suitable treatment options for individual patients are urgently needed to improve the dismal outcome of PDAC patients. Recently, alterations of Kisspeptin serum levels, a member of the adipokine family, were described in various types of cancers. However, the role of circulating Kisspeptin as a biomarker in PDAC patients is poorly defined. In this study, we measured Kisspeptin serum levels in a cohort of 128 prospectively enrolled PDAC patients undergoing surgical resection as well as 36 healthy controls. Kisspeptin concentrations were elevated in PDAC patients compared to control samples. Nevertheless, Kisspeptin serum levels were independent of tumor-related factors such as the tumor grading, TNM stage, or clinical features such as the ECOG performance status. Finally, in our analysis, neither preoperative nor postoperative Kisspeptin levels turned out as a significant predictor of overall survival after tumor resection. In conclusion, our data suggest that Kisspeptin concentrations are altered in PDAC patients but do not allow to predict patients’ outcome after resection of PDAC.

scholarly journals Levels of Circulating PD-L1 Are Decreased in Patients with Resectable Cholangiocarcinoma

2021 ◽  
Vol 22 (12) ◽  
pp. 6569
Author(s):  
Christoph Roderburg ◽  
Sven H. Loosen ◽  
Jan Bednarsch ◽  
Patrick H. Alizai ◽  
Anjali A. Roeth ◽  
...  
Keyword(s):  
Tumor Recurrence ◽  
Tumor Biology ◽  
Tumor Resection ◽  
Postoperative Outcome ◽  
Serum Levels ◽  
Strong Trend ◽  
Programmed Cell Death 1 ◽  
Early Tumor ◽  
Circulating Levels

Tumor resection represents the only curative treatment option for patients with biliary tract cancers (BTCs), including intrahepatic cholangiocarcinoma (CCA), perihilar and extrahepatic CCA and gallbladder cancer. However, many patients develop early tumor recurrence and are unlikely to benefit from surgery. Therefore, markers to identify ideal surgical candidates are urgently needed. Circulating programmed cell death 1 ligand 1 (PD-L1) has recently been associated with different malignancies, including pancreatic cancer which closely resembles BTC in terms of patients’ prognosis and tumor biology. Here, we aim at evaluating a potential role of circulating PD-L1 as a novel biomarker for resectable BTC. Methods: Serum levels of PD-L1 were analyzed by ELISA in 73 BTC patients and 42 healthy controls. Results: Circulating levels of preoperative PD-L1 were significantly lower in patients with BTC compared to controls. Patients with low PD-L1 levels displayed a strong trend towards an impaired prognosis, and circulating PD-L1 was negatively correlated with experimental markers of promalignant tumor characteristics such as CCL1, CCL21, CCL25 and CCL26. For 37 out of 73 patients, postoperative PD-L1 levels were available. Interestingly, after tumor resection, circulating PD-L1 raised to almost normal levels. Notably, patients with further decreasing PD-L1 concentrations after surgery showed a trend towards an impaired postoperative outcome. Conclusion: Circulating PD-L1 levels were decreased in patients with resectable BTC. Lack of normalization of PD-L1 levels after surgery might identify patients at high risk for tumor recurrence or adverse outcome.

Prognostic role of ECOG performance status in patients with urothelial carcinoma of the upper urinary tract: an international study

2011 ◽  
Vol 109 (8) ◽  
pp. 1155-1161 ◽  
Author(s):  
Juan Ignacio Martinez-Salamanca ◽  
Shahrokh F. Shariat ◽  
Joaquin Carballido Rodriguez ◽  
Thomas F. Chromecki ◽  
Vincenzo Ficarra ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Urothelial Carcinoma ◽  
Performance Status ◽  
International Study ◽  
Upper Urinary Tract ◽  
Prognostic Role ◽  
Ecog Performance Status

scholarly journals Nucleases as molecular targets for cancer diagnosis

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Alien Balian ◽  
Frank J. Hernandez
Keyword(s):  
Enzymatic Activity ◽  
Cancer Diagnosis ◽  
Essential Feature ◽  
Treatment Options ◽  
Cancer Biomarkers ◽  
Diagnostic Biomarkers ◽  
Early Cancer Diagnosis ◽  
Novel Biomarkers ◽  
Made In

AbstractEarly cancer diagnosis is a crucial element to improved treatment options and survival. Great research efforts have been made in the search for better performing cancer diagnostic biomarkers. However, the quest continues as novel biomarkers with high accuracy for an early diagnosis remain an unmet clinical need. Nucleases, which are enzymes capable of cleaving nucleic acids, have been long considered as potential cancer biomarkers. The implications of nucleases are key for biological functions, their presence in different cellular counterparts and catalytic activity led the enthusiasm towards investigating the role of nucleases as promising cancer biomarkers. However, the most essential feature of these proteins, which is their enzymatic activity, has not been fully exploited. This review discusses nucleases interrogated as cancer biomarkers, providing a glimpse of their physiological roles. Moreover, it highlights the potential of harnessing the enzymatic activity of cancer-associated nucleases as a novel diagnostic biomarker using nucleic acid probes as substrates.

Phase II study of irinotecan and paclitaxel for patients with recurrent small cell lung cancer (SCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18011-18011
Author(s):  
T. K. Owonikoko ◽  
S. Ramalingam ◽  
J. Forster ◽  
Y. Shuai ◽  
T. Evans ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Treatment Options ◽  
Objective Response ◽  
Ecog Performance Status ◽  
Stage Design ◽  
Prior Chemotherapy Regimen ◽  
Version 2.0

18011 Background: Recurrent SCLC has a poor prognosis and is devoid of treatment options that improve overall survival. Irinotecan and paclitaxel are both active agents against SCLC, and have synergistic preclinical interactions. We conducted a phase II study to evaluate the efficacy and safety of the combination of irinotecan and paclitaxel for patients with recurrent SCLC. Methods: Patients with SCLC who relapsed following one prior chemotherapy regimen were eligible. Other pertinent inclusion criteria were: ECOG performance status 0–2, adequate bone marrow, hepatic and renal function and willingness to provide informed consent. Patients with untreated brain metastasis were excluded. Paclitaxel (75 mg/m2) and irinotecan (50 mg/m2) were administered on days 1 & 8 of every 3-week cycle. Treatment was continued until progression up to a maximum of 6 cycles or unacceptable toxicity. The primary endpoint was response rate. Toxicity was graded by CTC version 2.0. The simon two-stage design was utilized and the estimated sample size was 55 patients (stage I - 23 patients; stage 2 - 32 patients). The study has a 90% power to detect a response rate of 30%, with an alpha error rate of 10%. Results: 55 patients have been enrolled and complete data are available for 32 patients at the time of this report. Patient baseline characteristics are: male 53%, PS 0–44%; PS 1–47% and PS 2–6%. The median age is 61 years. Fifteen patients received ≥ 4 cycles. Salient grades 3–5 toxicities seen: neutropenia (13%), fatigue (13%); diarrhea (3%), hypersensitivity (3%) and hyponatremia (3%).The objective response rate is 37% (95% CI 19%-55%) with 9 PRs and 1 CR. Additional 8 patients (24%) had stable disease. The median survival is 19.6 weeks (95% CI 15.1–29.4) and the 1-year survival rate is 15%. Conclusions: The combination of irinotecan and paclitaxel is well tolerated and has promising anti-cancer activity in recurrent SCLC. Updated data on all 55 patients will be available at the time of the presentation. No significant financial relationships to disclose.

Glioblastoma (GBM) in elderly patients: A randomized phase III trial comparing survival in patients treated with 6-week radiotherapy (RT) versus hypofractionated RT over 2 weeks versus temozolomide single-agent chemotherapy (TMZ).

2010 ◽  
Vol 28 (18_suppl) ◽  
pp. LBA2002-LBA2002 ◽  
Author(s):  
A. Malmstrom ◽  
B. H. Grønberg ◽  
R. Stupp ◽  
C. Marosi ◽  
D. Frappaz ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Survival Data ◽  
Treatment Time ◽  
Performance Status ◽  
Treatment Options ◽  
Single Agent ◽  
Tumor Resection ◽  
Phase Iii ◽  
Primary Study ◽  
Significant Difference

LBA2002 Background: Despite treatment advances, survival of elderly GBM patients (pts) is usually < 12 months. Hypofractionated RT is advocated in order to shorten treatment time, and chemotherapy has been proposed as an alternative to RT. In a randomized trial we compared two different RT schedules with single-agent TMZ chemotherapy. Methods: Newly diagnosed GBM pts age ≥ 60 years with PS 0-2, were randomized to either standard RT (60 Gy in 2 Gy fractions over 6 weeks) or hypofractionated RT (34 Gy in 3,4 Gy fractions over 2 weeks) or 6 cycles of chemotherapy with TMZ (200 mg/m2 day 1-5 every 28 days). Follow-up including quality of life, symptom checklist, and steroid dosing was completed at 6 weeks, 3 months, and 6 months after start of treatment. The primary study end point was overall survival (OS). Results: A total of 342 pts were included. 291 pts were randomized between the 3 treatment options, 51 pts between hypofractionated RT and TMZ. Median age was 70 years (range 60-88), 59% were male and 72% had undergone tumor resection, the remaining 28% had a diagnostic biopsy only. Performance status was 0-1 for 75% of pts. Survival data are available for 334 pts (98%), with 11 pts (3%) being alive. There was no significant difference in OS between the three treatment arms, with median survival being 8 months for TMZ, 7.5 months for hypofractionated RT and 6 months for 6 weeks RT (p=0.14). Conclusions: Elderly patients with GBM have a short survival. Time-consuming therapy that does not offer longer survival should therefore be avoided. Our study showed no advantage of standard 6 weeks RT compared to hypofractionated RT over 2 weeks or 6 cycles of TMZ chemotherapy. These results indicate that standard RT should no longer be offered to the elderly pt population with GBM. Exclusive TMZ chemotherapy may be an alternative to RT. Subgroup analyses and determination of molecular markers is ongoing. Whether outcome could be improved by concomitant chemoradiotherapy is subject of ongoing clinical trials. [Table: see text]

Clinical correlates of response to anti-PD-1 (aPD1)-based therapy in patients (pts) with metastatic melanoma (MM).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21000-e21000
Author(s):  
Elizabeth J. Davis ◽  
Shilin Zhao ◽  
Fei Ye ◽  
Katherine Rappazzo ◽  
Jeffrey Alan Sosman ◽  
...  
Keyword(s):  
Performance Status ◽  
Progression Free Survival ◽  
Clinical Predictors ◽  
Ecog Performance Status ◽  
Free Survival ◽  
Size Number ◽  
Multivariable Analyses ◽  
Status Number ◽  
Univariate Analyses ◽  
Selection Of

e21000 Background: aPD1, alone or in combination with ipilimumab (IPI), produces durable responses in a subset of MM. Tumor features that correlate with treatment response, including size, number, and location of metastases (mets) are not well defined. Methods: We collected clinical data from mm pts treated at one center who received aPD1 (n = 185) or aPD1 + IPI (n = 42). We correlated number of mets, size of largest tumor, and organ involvement with response rate (RR), progression-free survival (PFS) and overall survival (OS). Results: Among all pts, RR was 67% for aPD1 + IPI and 41% for aPD1 alone. In univariate analyses, responders to aPD1 had lower diameter of largest tumor (4cm vs. 5.5cm; p = 0.02) whereas aPD1 + IPI had equivalent largest tumor diameters (p = 0.65). Regarding sites of mets, liver mets were associated with lower RR in aPD1 treated pts (26% vs. 46%), lower PFS (median 138 vs. 326 days, p = 0.02), and lower OS (median 334 vs. 1080 days, p < 0.01). No associations with RR, PFS, or OS were observed with liver mets in aPD1 + IPI treated pts. We also did not observe any differences between pts who did or did not have lung, lymph node, or brain mets for either aPD1 or aPD1 + IPI. Interestingly, superior RR to aPD1 + IPI was observed in pts with bone mets compared to those without bone mets (91% vs. 58%, p = 0.048). Regarding number of sites, RR to aPD1 was greater in pts with ≤10 mets compared with those with > 10 (46% vs. 28%, p = 0.02), although no consistent relationship was observed at lower cutoffs. In multivariable analyses, diameter of largest tumor (tumor bulk) was independently associated with PFS (OR, 1.11, p < 0.001) and OS (OR 1.08, p < 0.001) whereas AJCC stage, lactate dehydrogenase, liver mets, ECOG performance status, number of mets, and prior therapies were not significant. Tumor bulk and other risk factors were not associated with PFS or OS in aPD1 + IPI. Conclusions: Tumor bulk was strongly and independently associated with clinical outcomes in aPD1 but not IPI + aPD1. Other associations with disease sites (liver and bone) need further validation. In conjunction with molecular biomarkers, clinical predictors may help guide selection of aPD1 or aPD1 + IPI.

Soluble urokinase plasminogen activator receptor (suPAR) as a novel biomarker in patients undergoing resection of pancreatic adenocarcinoma.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 248-248
Author(s):  
Sven H Loosen ◽  
Marcel Binnebösel ◽  
Thomas Longerich ◽  
Christoph Roderburg ◽  
Christian Trautwein ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Pancreatic Adenocarcinoma ◽  
Tumor Resection ◽  
Serum Levels ◽  
Healthy Controls ◽  
Urokinase Plasminogen Activator Receptor ◽  
Tissue Samples ◽  
Pdac Tissue ◽  
Plasminogen Activator Receptor

248 Background: Surgical resection represents the only potentially curative therapy for patients with pancreatic adenocarcinoma (PDAC), an aggressive malignancy with a very limited 5-year survival rate. However, even after successful R0 tumor resection, some patients are still facing an unfavourable prognosis underlining the need for better preoperative stratification algorithms. The soluble urokinase plasminogen activator receptor (suPAR) was recently described as a promising new biomarker for different clinical conditions including cancer. Here, we evaluated the potential role of circulating suPAR as a biomarker in patients undergoing resection of PDAC. Methods: Expression levels of uPAR, the membrane-bound source of circulating suPAR, were analysed in PDAC tissue samples using IHC. Serum levels of suPAR were measured by ELISA in an exploratory as well as a validation cohort comprising a total of 127 PDAC patients and 75 healthy controls. Results were correlated with clinical data. Results: Correlating with a high immunohistochemical expression of uPAR in PDAC tissue samples, serum levels of suPAR were significantly elevated in PDAC patients compared to healthy controls. Importantly, patients with high preoperative suPAR levels above a calculated cut-off value of 5.956 ng/ml showed a significantly reduced overall survival after tumor resection. The prognostic role of suPAR was further corroborated by uni- and multivariate Cox-regression analyses including parameters of systemic inflammation, liver and kidney function as well as clinico-pathological patients’ characteristics. Moreover, high baseline suPAR levels identified those patients particularly susceptible to acute kidney injury after surgery. Conclusions: Our data suggest that circulating suPAR represents a novel prognostic marker in PDAC patients undergoing tumor resection that might be a useful addition to existing preoperative stratification algorithms for identifying patients that particularly benefit from extended tumor resection.

Cancer-associated venous thromboembolism: Burden, mechanisms, and management

2017 ◽  
Vol 117 (02) ◽  
pp. 219-230 ◽  
Author(s):  
Cihan Ay ◽  
Ingrid Pabinger ◽  
Alexander T. Cohen
Keyword(s):  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Performance Status ◽  
Direct Oral Anticoagulants ◽  
Treatment Options ◽  
Cancer Site ◽  
Related Factors ◽  
Venous Diseases

SummaryVenous thromboembolism (VTE) is a significant health problem in the general population but especially in cancer patients. In this review, we discuss the epidemiology and burden of the disease, the pathophysiology of cancer-associated VTE, and the clinical treatment options for both primary prevention and acute treatment. Overall, the development of VTE in cancer patients is related to increases in morbidity, mortality, and medical costs. However, the incidence of cancer-associated VTE varies due to patient-related factors (e.g. thrombophilia, comorbidities, performance status, history of venous diseases), tumour-related factors (e.g. cancer site, stage, grade), and treatment-related factors (e.g. surgery, chemotherapy, anti-angiogenesis treatment, hormonal and supportive treatment). Furthermore, blood count parameters (e.g. platelets and leukocytes) and biomarkers (e.g. soluble P-selectin and D-dimer) are predictive markers for the risk of VTE in cancer patients and have been used to enhance risk stratification. Evidence suggests that cancer itself is associated with a state of hypercoagulability, driven in part by the release of procoagulant factors, such as tissue factor, from malignant tissue as well as by inflammation-driven activation of endothelial cells, platelets, and leukocytes. In general, low-molecular-weight heparin (LWMH) monotherapy is the standard of care for the management of cancer-associated VTE, as vitamin K antagonists are less effective in cancer patients. Direct oral anticoagulants (DOACs) offer a potentially promising treatment option for cancer patients with VTE, but recommendations concerning the routine use of DOACs should await head-to-head studies with LMWH.

scholarly journals Treatment Patterns and Outcomes Among Elderly Glioblastoma Patients at KFMC, Riyadh.

2021 ◽  
Author(s):  
Amal Maire ◽  
Ahmed M. Maklad ◽  
Abdullah Altwairqi ◽  
Wafaa AlShakweer ◽  
Mohamed Senosi ◽  
...  
Keyword(s):  
Adjuvant Treatment ◽  
Performance Status ◽  
Treatment Options ◽  
Univariate Analysis ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
Treatment Patterns ◽  
Subtotal Resection ◽  
Ecog Performance Status ◽  
Significant Factors

Abstract IntroductionManagement of elderly patients with cancer is a controversial scenario and needs careful assessment and selection for aggressive radical treatment and chemotherapy protocols versus short-course radiotherapy without chemotherapy. Of note, definitions of the elderly vary in the glioblastoma (GBM) literature, with most of the randomized trials including patients aged 60, 65, or 70 years or older.Aim of the workTo evaluate treatment patterns and outcome among elderly GBM patients treated in KFMC, Riyadh. The primary endpoint is overall survival (OS) and the Secondary endpoint is progression-free survival (PFS) in relation to different treatment options and prognostic factors. MethodsThis is a retrospective study, included elderly GBM patients treated at KFMC, Riyadh, KSA between 1/2008 till 1/2018. 59 patients diagnosed with GBM ≥ 60 years were reviewed regarding radiotherapy (Rth) fractionation modalities, surgery, and chemotherapy (CTR) given in correlation to PFS, OS.Results59 patients were recruited in our study with median age 66 range (60-81) years, 47 (80%) were males. 37 patients (62.7%) had Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥2, and 22 patients (37.3%) had PS < 2. Gross total resection (GTR) and subtotal resection (STR) was done in 49 (82.9%) patients, and the median follow-up was 12 months.38 (64%) patients received conventional Rth 60 Gray (Gy)/30 fractions or equal doses and 21 (36%) patients received hypofractionation Rth (40 Gy/15, 25 Gy/5 or 30 Gy/10 fractions).The median OS was 12 months (95% CI,9.52-14.48). For univariate analysis, receiving a conventional Rth and completion of 6 months adjuvant CTR were significant factors for O.S (P= 0.043 and 0.026) respectively. For multivariate those were also significant (P=0.035 and 0.002) respectively.The median PFS was 9 months (95% CI, 6.13-11.87). For univariate analysis PS, time to start adjuvant treatment, and completion of 6 months CTR were significant factors for PFS. For multivariate analysis starting adjuvant treatment within 2 months and completed CTR 6 months were significant factors (P=0.032 and 0.04) respectively. ConclusionElderly GBM patients who received conventional Rth and completed adjuvant 6 months CTR achieved a better OS, while starting adjuvant treatment earlier than 2 months and completed adjuvant CTR 6 months were associated with a better PFS, further prospective studies are needed to confirm our finding.

scholarly journals Association of HMGB1, S100A12 and IL-17A Expression with IVIG-Resistant Kawasaki Disease and Treatment Options

2020 ◽  
Author(s):  
Deying Liu ◽  
Pan Liu ◽  
Fan Liu ◽  
Wei Yin ◽  
Yan Ding
Keyword(s):  
Kawasaki Disease ◽  
Coronary Arteries ◽  
Adjunctive Therapy ◽  
Clinical Symptoms ◽  
Treatment Options ◽  
Poor Response ◽  
Serum Levels ◽  
Laboratory Parameters ◽  
Molecular Pattern

Abstract Background: Kawasaki disease (KD) is a medium vessel vasculitis of unknown aetiology that predominantly affecting coronary arteries. The damage-associated molecular pattern molecules (DAMPs) such as HMGB1, S100A12 and IL-17A have been reported to predict poor response to IVIG. Here, we explored the the role of HMGB1, S100A12 and IL-17A in the detection of intravenous immunoglobulin (IVIG)-resistant in KD patients, and to investigate the value of different adjunctive therapy.Method: 126 KD patients and as well as age- and sex-matched 16 febrile control subjects were enrolled in our study. The fresh peripheral blood were collected from KD patients and febrile controls, analyzed the demographic or clinical data and various laboratory parameters. We also measured changes in serum levels of IL-17A and mRNA expression levels of HMGB1 and S100A12 were tested in IVIG-resistant KD patients. Further we explored the association between coronary arteries lesions and different treatment options about IVIG retreatment, methylprednisolone and infliximab for IVIG-resistant KD patients. Result: Regarding laboratory parameters, KD individuals were found to have lower levels of lymphocyte(L)%, prealbumin, CD4+, CD8+ and higher levels of WBC, neutrophil (N)%, CRP, ESR, NT-proBNP, ALT, CD4+/CD8+ (P<0.05 or P<0.01). For KD group, the 53 IVIG-resistant patients had significantly higher levels of S100A12, HMGB1, serum IL-17A, N%, CRP, NT-proBNP, TBIL, ALT, AST and lower levels of L%, PLT (P<0.05 or P<0.01) in comparison to the IVIG-responsive patients. For patients with IVIG-resistant, IVIG retreatment, methylprednisolone or infliximab were used. Methylprednisolone showed better in improving clinical symptoms and CRP than the IVIG retreatment and infliximab (P> 0.05).Conclusion: IVIG-resistant was associated with overreaction of inflammation.The levels of HMGB1,S100A12 and IL-17A suggested to be reliable predictors for IVIG-resistant in KD. In addition, the adjunctive therapy of methylprednisolone and infliximab showed more effective in relieving clinical symptoms than IVIG retreatment.

Sign in / Sign up

Export Citation Format

Share Document