bluuebunny/crossref_metadata_2025 huggingface dataset:
Pananemia 2008 multicenter observational study on erythropoietin beta treatment in patients with cancer: Efficacy, patient satisfaction, and impact on psychological distress
Authors: Del Prete S. , Addeo R. , Leo L. , Cinieri S. , Lorusso V. , Vincenzi B. , Bianco M. , Savastano C. , Montesarchio V. , Filippelli G. ,   Pananemia Southern Italy Group GOIM
Published: August 2020

e20695

Background: Cancer-related anemia, results in both a need for transfusions and a decreased functional capacity and quality of life. Treating anemia associated with chemotherapy and many cancers is often necessary. However, patient satisfaction with anemia treatment, and the possible correlation between anemia and psychological distress frequently present in these patients is limited by the lack of validated instruments. Methods: Between January 2008 and December 2008, 591 cancer patients in treatment with erythropoietin beta for anemia were targeted to complete the Psychological Distress Inventory (PDI), a 13-item self-administered questionnaire, and the Patient Satisfaction Questionnaire ( PSQ) at 4 week intervals, a 10-item, self-administered questionnaire. Data from weeks 5 and 9 were analyzed. Patients were required to receive at least four weekly injections of Epo, expecting to receive ≥ 8 additional weeks of chemotherapy, and able to complete questionnaires. Results: Among patients fulfilling eligibility criteria and having received at least four Epo Beta administrations, most (57.5%) of them were female, with a median age of 66 (52.4 - 76.5), and a median KPS of 85 (range: 50–100). 399 patients had a stage IV cancers. Hemoglobin values increased from mean baseline levels of 9.55 g/dL, to attain levels 10.31 at week 5, and 11.05 after 8 weeks of therapy; 247 (42%) patients received iron supplementation. For PDI, the overall response rate was 93 % (548/591) at baseline, 100 % (517/517) at week 5, and 99% (491/492) at week 9. The percentage of patients with psychological difficulties decreased during the treatment. For PSQ, the overall response rate was 100% (517/517) at week 5, and 100 % (492/492) at week 9. The PSQ questionnaires showed that a conspicuous group of patients (124/517) marked troubles to accept the treatment. Conclusions: Our results suggest that in anemic cancer patients psychological distress and anemia were related. PSQ reflect the burden of injection anemia treatment on cancer patients. Final data analysis will be presented.

No significant financial relationships to disclose.
Analysis of the patient-related barriers in cancer pain anagement in Turkish patients
Authors: Bagçivan G. , Tosun N. , Kömürcü S. , Özet A. , Akbayrak N.
Published: August 2020

e20699

Background: The most important issue, which may be preventing effective cancer pain management, have generally been the barriers originating from misbelieve or misunderstandings, which lead patients to be reluctant to report pain and receive the appropriate analgesic. It is the first study about this issue in Turkey. Methods: This study was planned as a descriptive and cross-sectional. The sample was 170 patients with cancer, who used or is still using analgesic medication for pain related to cancer. Demographic Questionnaire, Brief Pain Inventory and BQ-II were used for data collection. The reliability coefficient for the total scale and subscales (Cronbach's α) were calculated. Test and retest results were compared to determine the scales validity for Turkish patients. All statistical analyses were performed with the SPSS 15.0.The value p≤0.05 was considered ‘statistically significant’. Results: As a result of the factor analysis made for BQ-II, seven factors that make up for 66.451% of the total variance were found. Cronbach's alpha value was 0.87 for the BQ-II. According to the points given by patients to the items in BQ-II, it was seen that they have beliefs that may be barriers to optimal pain management mostly in “addiction” and minimally in “physical side effects” subscale. It was ascertained that male, not married patients, patients with a chronic disease other than cancer, patients whose “average pain” level is >5 and who use inadequate analgesic have more beliefs that may be barriers to optimal pain management. Conclusions: BQ-II was a valid and reliable scale for Turkish defining patient related barriers in cancer pain management. Items suggested by patients such as “family related barriers” and “family members’ role and responsibilities” could be added to the BQ-II for future studies.

No significant financial relationships to disclose.
Adverse events due to chemotherapy in emergency room
Authors: Serrano Solares S. , Vidal M. , Ferrer A. , Tobeña M. , Millastre E. , Ruiz Echarri M. , Pajares I. , Lopez D. , Tres A. , Lambea J.
Published: August 2020

e20701

Background: High rates of mortality due to cancer make necessary improve oncologic treatments. Relationship between adverse events and chemotherapy schedule and dose is well known thanks to large observational studies. Our study´s objective is to estimate the prevalence of chemotherapy adverse events in oncologic patients attended in Emergency room. Methods: From October 2007 to October 2008 560 patients were recollected. It was revised tumors location and stage, chemotherapy schedule and date of the last treatment, diagnosis and therapheutic in Emergency. Results: 87 of the 560 patients (15%) were attended in Emergency room because of chemotherapy toxicity. The most common cause of consultation was fever (27 patients, 31%) followed by diarrhea (18 patients, 20.7%) and nausea-vomiting (12 patients, 13.8%). Most of the patients were being treated with classic chemotherapy schedules (70.1%). Comparing as a whole all the chemotherapy schedules there were not statistically significant differences due to toxicity between them. Nevertheless analyzing by subgroups we found there was no difference between toxicity in patients treated with classic chemotherapy and chemotherapy plus target agents (33.8% vs 5.5%, p=0.30), but there was differences between chemotherapy and target agents in monotherapy (33.8% vs 13.2%, p<0.05). In 39 of the 87 patients (39%) admission was required with a good evolution in most of them. Conclusions: Adverse events due to chemotherapy is a common cause of consultation in Emergency room. In our sample new target agents did not add toxicity to classic chemotherapy and given as monotherapy they had really good tolerance. More randomized studies are necessary to do a better evaluation of adverse events due to new agents.

No significant financial relationships to disclose.
Fever in cancer patients as a cause of attendance in emergency room
Authors: Vidal M. , Ferrer A. , Serrano S. , Tobeña M. , Pajares I. , Lopez D. , Millastre E. , Ruiz-Echarri M. , Lambea J. , Tres A.
Published: August 2020

e20706

Background: Normal human body temperature displays a circadian rhythm, ranging from 36.1 C or lower in predawn hours to 37.4 C or higher in the afternoon. Abnormal elevation of temperature occurs as a result of hyperthermia or fever. Cancer patients frequently experience fever. Nearly two-thirds of the cases of fever in patients with prolonged neutropenia could be attributed to infection, a major cause of morbidity in cancer patients. Purpose: The aim of our study is to evaluate the prevalence of cancer patients who were attended in the emergency room for fever, the diagnosis and clinical management. Methods: From October 2007 to October 2008, 560 cancer patients were seen in the emergency department of the University Hospital of Zaragoza. The purpose of this paper is to describe the characteristics of patients who presented with fever. Results: A total of 560 patients were seen. Ninety-eight (17.5%) presented with fever. 63% of patients were stage IV. Cancer tumor type, 35 had lung cancer (35.7%), 14 had breast cancer (14.3%), 9 had colorectal cancer (9.2%), 9 had urothelial cancer (9.2%), 5 had head neck cancer (5.1%), 5 had pancreatic cancer (5.1%), 3 had esophageal cancer (3%), 2 had prostate cancer (2%), and 14,3% had other neoplasm. 18 patients (18.36%) had been received chemotherapy treatment in a period of 10 days before. they were attended in emergency room. By diagnosis: 23 patients (23,46%) were diagnosed of febrile neutropenia, and 19 of them (82,6%) required admission to the hospital. 30 were diagnosed of respiratory tract infection (30,6%), 12 were diagnosed of urinary infection (12.24%). Considering all the patients who presented with fever: 45 patients were sent home with new treatment (45,9%), 6 patients were observed for 24 hours in the emergency room (6.2%) and 47 patients required admission to the hospital (47.9%). Conclusions: Fever in cancer patients remains a challenge, and the differentiation between infectious and non-infectious causes at onset of fever is very difficult. Despite all the prophylactic measures, infection is still the principal cause. Infection in the immunocompromised host is a serious clinical situation due to high morbimortality and is one of the most frequent complications in the patient with cancer.

No significant financial relationships to disclose.
A randomized controlled trial of the effect of intercessory prayer on the spiritual wellbeing and quality of life of patients with cancer
Authors: Olver I. N. , Whitford H. S.
Published: August 2020

e20708

Background: A number of scientific trials assessing the positive impact of intercessory prayer attest to centuries of anecdotal evidence, despite debate of its mechanism. However, little attention has been afforded to patients with cancer and the effect such intervention has on quality of life, including spiritual wellbeing. This study aimed to assess the effect of remote, Christian intercessory prayer on cancer patients’ quality of life, specifically their spiritual wellbeing, including their search for meaning, peace, and faith. Methods: New, consecutive patients with cancer attending an Australian cancer centre, aged 18 years or above, able to read English, and give consent were recruited. With Ethics Committee approval, this prospective, double blinded randomized controlled trial only partially divulged the nature of the study to patients who were informed of the measurements but not the inclusion of randomization to an intervention. Specifically, patients were blindly, randomly allocated to receive distant, intercessory prayer from an established Christian prayer chain (intervention) or not to receive prayer (control). All patients completed the Mental Adjustment to Cancer (MAC) scale and the Functional Assessment of Chronic Illness Therapy - Spiritual Well-Being (FACIT-Sp) at baseline. The FACIT-Sp was re-administered six months later to assess the primary endpoint, a change in spiritual wellbeing. It was anticipated that 1000 patients were needed (allowing for 20% drop out) to achieve 80% power to detect hypothesized small differences (Cohen's d .20-.50) between groups (alpha = .05). Results: A total of 1003 eligible, consenting patients were accrued between June 2003 and May 2008. Intervention (n = 509) and control (n = 494) groups will be compared across baseline characteristics to identify any pre-existing differences. Between-within subject analyses of covariance (ANCOVAs) will be used to assess whether any differences were evident between groups across measures of spiritual wellbeing and other facets of quality of life. Conclusions: The results of these analyses will be presented. It is hoped this research will provide further empirical support for the biopsychosocialspiritual model of health.

No significant financial relationships to disclose.
History and organization of palliative care in Poland
Authors: Swietlik E. , Doboszynska A.
Published: August 2020

e20749

Beginning of the hospice care in Poland is associated with democratic opposition in the eighties of the XX century and social movement Solidarity. In 1978, C. Saunders visited Gdansk, Warsaw, and Krakow, supporting an organization of palliative care in Poland. Polish hospice care, similarly to other countries,originated from the necessity of special care of terminally ill cancer patients. Palliative care societies, initially informal, then registered formally, emerged in Poland in 1981. Hospices, both institutional and house hospice care, came into being in all larger cities in Poland to the nineties of the XX century. In 1991, National Forum of the Hospice Movement was founded. This Forum, gathering the majority of hospices, is actually transformed into the association of societies: Forum of the Polish Hospices. In the nineties of the XX century, professional palliative care developed. Since 1998, specialization in the palliative care for both physicians and nurses is available. From the very beginning, hospice care based on the volunteers gathered at the Roman Catholic parish and several priests first organized palliative care. In 1991, The Sejm (lower chamber of the Polish Parliament) passed the law Health care institutions, enabling various societies and associations to establish health care institutions, whereas the law The Social Insurance Act (1997) gives an opportunity to get financial means for hospice care from the State. Actually, there are hospices acting on voluntary service (the number of such hospices decreases), partial voluntary service and also paid employees, and institutions which activities are based on full-time employment and financed by the National Health Fund. About 130 non-profit societies and hospice foundations both secular andchurch exist in Poland. Non-public health care institutions founded 99 hospices. About 70 hospices (both public and private) are stationary.

No significant financial relationships to disclose.
Spectrum of KIT and PDGFRA mutations in primary gastrointestinal stromal tumors: Polish Clinical GIST Registry experience
Authors: Wozniak A. , Rutkowski P. , Debiec-Rychter M. , Siedlecki J. , Michej W. , Osuch C. , Matlok M. , Ruka W. , Limon J. ,   Polish Clinical GIST Registry
Published: August 2020

e21504

Background: KIT or PDGFRA gene mutations are found in 80–90% of gastrointestinal stromal tumors (GIST). The prognostic value of those mutations for the outcome in primary tumors is controversial. Objective: To assess the spectrum, frequency and prognostic significance of the KIT and PDGFRA gene mutations in Polish group of surgically treated primary GISTs. Methods: DNA isolated from paraffin blocks from 300 patients (pts) with histologically diagnosed primary GISTs included in clinical registry database, were analyzed using denaturing high performance liquid chromatography (DHPLC) and direct sequencing for KIT (exons 9, 11, 13, 17) and PDGFRA (exons 12, 14, 18) mutations. For primary GIST risk assessment the Miettinen stratification was used. Results: KIT/PDGFRA genes mutations were found in 82% tumors: KIT was mutated in 69% and PDGFRA in 13% of tumors. KIT exon 11 and 9 mutations were found in 61.5% and 7.5% respectively. Among KIT exon 11 mutants the most frequent were deletions (32.7%) followed by point mutations (15.3%), duplications (8.4%) and complex rearrangements (5.1%). KIT exon 11 mutations were found at the similar rates in tumors with gastric and non-gastric localization (53.9% vs. 46.1% respectively) while KIT exon 9 duplications were more often observed in non-gastric GISTs (86.4%, p=0.00036) and PDGFRA mutations were more frequently found in tumors originated from the stomach (86.8%; p=0.00017). In high risk tumors KIT exon 11 deletions were more frequently found than point mutations (p=0.017). On the other hand mutations in PDGFRA were more often observed in very low-/low- than high risk GISTs as compared to KIT exon 11 (p=0.0026). There was no statistically significant correlation between disease-free survival and the spectrum or frequency of mutations. Conclusions: Spectrum and frequency of KIT and PDGFRA mutations in Polish GIST population are similar to the previously described groups. No significance of mutations for disease outcome after surgery of primary tumors was found.

[Table: see text]
Evaluation of Ki-67 in gastrointestinal stromal tumor (GIST)
Authors: Saponara M. , Di Battista M. , Lolli C. , Derenzini E. , Pantaleo M. A. , Santini D. , Ceccarelli C. , Catena F. , Nannini M. , Maleddu A. , Biasco G.
Published: August 2020

e21510

Background: GISTs show a wide spectrum of biological behaviors which translates in an even wider spectrum of possible clinical courses. The two canonical parameters used for the prediction of GISTs’ prognosis are tumor size and mitotic index. However, few but controversial data on Ki-67 are also available. The aim of our study was to clarify the role of Ki-67 expression as a new biological marker in GISTs. Methods: Forty-one cases of GIST were examined. Twenty-six cases arose from stomach and 15 from small bowel. Immunohistochemical analysis for Ki-67 was stained on tissue samples and a cut-off value of >10% immunoreactive cells was used to distinguish between low (<= 10%) and high (>10%) Ki-67 nuclear expression. The expression of this cell-cycle related protein was correlated with tumor site (stomach; any other site), dimensions (<5 cm; >=5cm), mitotic index (<=5/50 HPFs; >5/50 HPFs), standard risk groups (low; intermediate-high) and disease free survival (DFS). Results: Ki-67 over-expression was positively correlated with tumor size >=5cm (p= 0.035). Not significant but a positive trend was seen with intermediate and high risk groups (p = 0.114), mitotic index >5/50 HPFs (p = 0.615). Lower levels of Ki-67 expression have been observed in gastric GISTs compared to any other site (29 cases with Ki-67 <=10% of which 21 gastric and 8 in other sites), even if these values were not statistically significant (p = 0.527). Moreover, Ki-67 over-expression was found to be significantly associated with a shorter DFS interval (p = 0.0196, analysis performed on 32 cases). Conclusions: Our data demonstrate that Ki-67 over-expression is significantly correlated with larger GIST and with a shorter DFS, suggesting that Ki-67 evaluation can be a useful tool to predict biological behavior of GIST, even if further studies are needed. In a clinical perspective, such information could be used in association with standard risk factors to select patients who could benefit from adjuvant therapy.

No significant financial relationships to disclose.
Clinical features and outcome in primary breast sarcomas (BS): Analysis of a single-institution experience
Authors: Ramon y Cajal T. , Mazarico J. , Lopez Pousa A. , Quintana M. , Sala N. , Altabas M. , Sebio A. , Robert L. , Alonso C. , Barnadas A.
Published: August 2020

e21520

Background: BS are characterised by local spread and recurrence. Controversy remains about local and adjuvant treatment. The objective of this retrospective study was to analyze clinical and pathological prognostic factors influencing the outcome of BS patients. Methods: We analyzed clinicopathological variables, treatment and outcome of 33 BS patients treated at our institution from 1966 to 2007. A single pathologist reviewed pathologic diagnoses. Kaplan Meier method was used to evaluate outcome. Mean age: 44 years (20–82y. Tumor size 57 (0–230) mm. Pathology: 17 cistosarcoma phylodes (CPh), 9 angiosarcoma, 2 extraesqueletical osteosarcoma, 2 fibrosarcomas, 1 liposarcoma, 1 leiomiosarcoma, 1 malignant fibrous histiocitoma (2.9%). Low-grade in 12, high-grade in 15 pts. Mastectomy in all but 8 patients. Adjuvant chemotherapy and radiotherapy in 9 and 7 patients. Pathological stage I- 12%, II- 65%, III- 9%, IV-3% Results: Median follow-up 71 (5–239) months. Median survival 160 months. Survival was 83%, 74% and 59% at 5, 10 and 15 year. 5/8 (62.5%) local excision patients needed rescue surgery due to local progression. 8/25 (32%) mastectomy patients progressed Local recurrence in 9 pts, distant 4 pts (radical rescue surgery in 10 pts). 7 pts death only 1 phyllodes. Mean 15-year survival for CPh was 169 vs 124 months for other histologies (p 0.06). In the univariate analysis we didn't found statistical differences according to clinical & pathological factors, stage and recurrence, on OS or PFS. Conclusions: CPh have better prognosis than other BS although its stage or size tends to be higher. Radical surgery in BS should be always considered as first treatment option. High-grade non-phylodes BS types may be considered for adjuvant chemotherapy although there were non-statistical differences in OS.

No significant financial relationships to disclose.
Activity of lenalidomide in metastatic hepatic epithelioid hemangioendothelioma (HEH): A case report
Authors: Schilling G. , Schuch G. , Panse J. P. , Sterneck M. , Bokemeyer C.
Published: August 2020

e21527

Background: HEH is a rare tumor of the liver with an unpredictable malignant potential. Surgical resection or liver transplantation is recommended in locally advanced disease and has been successfully performed in selected cases with extrahepatic manifestations. Systemic therapy, however, is not standardized. Small cohorts have been treated with interferon, chemotherapy and angiogenesis inhibitors such as thalidomide with various results. Case report: A 33-year old caucasian previously healthy male was admitted to hospital with newly diagnosed suspicious lesions in liver and spleen. Further analyses showed additional pulmonal nodules. Biopsy revealed a tumor with predominant epithelioid cells, positive for CD31 and CD34 and negative for CD117, HHV8, AFP and CEA, classified as a HEH. Disease progressed during first line treatment with adriamycin and ifosfamide (2 cycles given). Based on a case report with encouraging results with thalidomide we treated our patient with lenalidomide, which is known to have less side effects while being more effective in the myeloma setting. After 6 courses of lenalidomide 25mg daily (21/28), regression of the splenic lesions was detected. Retrospective analysis after 9 cycles demonstrated stable disease in comparison to the recent investigation, but an overall progression of 22% according to RECIST criteria in the liver was observed. Due to the excellent tolerance we increased the daily dose to 30 mg (21/28) and 6 months later a slight regression in the lung and overall stable disease in the liver was observed. The splenic lesion disappeared completely. The patient was listed for liver transplantation and after another 4 months on lenalidomide 30 mg, he was successfully transplanted recently. Because of the remaining extrahepatic lesions it is planned to continue lenalidomide therapy in combination with the immunosuppressant rapamycine. Conclusions: We report the first case of successful therapy with lenalidomide in HEH. Higher doses than 25mg seem to be more effective. We grateful thank Celgene for offering us lenalidomide for this off label use.

No significant financial relationships to disclose.
Clinical relevance of small tumor size (pT1a-b) for patients with HER2-positive, node-negative breast cancer
Authors: Curigliano G. , Fumagalli L. , Bagnardi V. , Rotmensz N. , Locatelli M. , Ghisini R. , Viale G. , Veronesi P. , Goldhirsch A.
Published: August 2020

e22011

Background: Prognosis of patients with node-negative, HER2-positive disease and tumor size ≤ 1 cm is a matter of controversy. We assessed the prognostic role of HER2 overexpression/amplification in a large series of patients with node-negative, pT1a,b breast cancers. Methods: All consecutive patients with pT1a,b pN0 M0 HER2-positive breast cancer who underwent surgery at the European Institute of Oncology (IEO) from 1995 to 2006 were identified. No patient received trastuzumab in the adjuvant setting. A matched cohort comparison was done using as variables hormone receptor status (positive vs. negative), age at surgery and year of surgery. Comparison group included patients with HER2-negative breast cancer matched 1:1 for hormone receptor negative group and 1:2 for hormone receptor positive group. We estimated rates of local recurrence, distant metastases, disease free survival (DFS) and overall survival (OS) in the hormone receptor positive and hormone receptor negative group. Results: We identified 150 patients with pT1a,b pN0 M0 HER2-positive tumors. The median follow-up was 4.6 years (range 1.0–9.0). In the hormone receptor positive group 5-year DFS was 99% [95% CI: 98%-100%] for HER2-negative and 92% [95% CI: 86%-99%] for HER2-positive disease. In the hormone receptor negative group 5-year DFS was 92% [95% CI: 84%-100%] for HER2-negative and 91% [95% CI: 84%-99%] in HER2-positive disease. Overall, for patients with hormone receptors positive and negative disease, the hazard ratio (HR) associated to HER2 overexpression was 2.4 (95% CI: 0.9–6.5, p=0.09). OS in HER2-positive pT1a,b pN0 M0 breast cancer was similar in hormone receptor positive and negative patients (p=0.93). Conclusions: Node-negative, HER2-positive, pT1a,b breast cancer have a low risk of locoregional and distant recurrence within the first 5 years after diagnosis. In patients with hormone receptor positive, pT1a,b N0 M0 tumors, HER2 overexpression seems to be associated with a dire prognosis (HR=5.2, 95% CI: 1.0–25.9) in terms of DFS.

No significant financial relationships to disclose.
Clinical implication of ERCC1 overexpression in advanced biliary tract adenocarcinoma patients treated with platinum-based palliative chemotherapy
Authors: Hwang I. , Chi K. , Do J. , Lee G. , Kang J. , Oh S. , Kwon H. , Park H. , Lee S. , Lee S. , Jang J.
Published: August 2020

e22018

Background: Several clinical studies have shown that Excision repair cross-complementation group1 (ERCC1) overexpression is associated with resistance to platinum-based chemotherapy and poor prognoses in several tumors. However these studies have never been tried for biliary tract cancer. The aim of this study was to evaluate the association between ERCC1 expression and treatment outcomes in advanced biliary tract adenocarcinoma patients treated with platinum-based palliative chemotherapy. Methods: We analyzed 45 patients with histologically confirmed adenocarcinoma of biliary tract at 5 institutions between January 2002 and March 2008. ERCC1 expression was assessed by immunohistochemistry from biopsy specimens. Results: ERCC1 expression was positive in 17 of 45 specimens (37.8%). 26 (57.8%) of 45 patients showed clinical benefits(including complete response, partial response and stable disease). Among 26 patients who obtained clinical benefits, seven (27%) were positive for ERCC1 expression and ninety (73%) were negative (p=0.079). With a median follow-up of 6.6 months (range, 0.9–39.4 months), median Progression free survival (PFS) and Overall survival (OS) were 4.4 months (95% CI, 3.2–5.6 months) and 8.5 months (95% CI, 6.1–10.9 months), respectively, for the total study population. On univariate analysis, PFS was 2.3 months for patients with ERCC1 positive tumor and 5.3 months for those with ERCC1 negative tumor (P = 0.053). However OS was significantly longer in the ERCC1-negative group than in the ERCC1-positive group (10.0 vs 4.4 months, respectively; P = 0.001). Other factors affecting the prolongation of OS were objective response rate (P = 0.016) and clinical benefits (P = 0.001). A Cox proportional hazard model showed that negative ERCC1 expression (hazard ratio 0.405, 95% CI, 0.200–0.820; P = 0.012) and clinical benefit (hazard ratio 0.183, 95% CI 0.080–0.420; P = 0.001) were significant independent prognostic factors for the prolongation of survival. Conclusions: These results suggest that advanced biliary tract adenocarcinoma patients with ERCC1-negative tumors show a survival benefit from palliative chemotherapy with a platinum- containing regimen.

No significant financial relationships to disclose.
Proteomics: A panel of seven serum biomarkers as a promising diagnostic tool for breast cancer
Authors: Lastra R. , Monasterio A. , Alvarez-Busto I. , Mayordomo J. , Algorta J. , de Juan A. , Pericás I. , Garijo F. , Aberro J. , Fernandez S. , Martín M.
Published: August 2020

e22019

Background: Conventionals serum biomarkets have a low sensibility in breast cancer diagnosis. Proteomic is a promising tool to identify new proteins profiles to be used in screening and early diagnosed. Methods: 1)Biomarker identification: Serum proteins from 114 women were separated and analysed by bidimensional gel electrophoresis; data from 72 patients (p) were compared with those from 42 control women to search for differentially expressed proteins. Several comparisons were performed between controls and p regarding clinical parameters such as histological type, tumour stage and lymph node affection (-/+). A total of 53 spots were found to be differentially expressed and identified by mass spectrometry (MS) as potential breast cancer biomarkers.2) Protein Chip development: A Protein Chip was developed with antibodies against six biomarkers and three control proteins (an antibody for the detection of a spiked control, for data normalization and two proteins as positive and negative controls). An antibody against CA15–3 antigen was also included as a reference breast tumour marker to be compared with our biomarker panel. 3) Clinical validation of the Protein Chip: A clinical validation study was carried out with 75 healthy women and 125 breast cancer p. After multivariate statistical analysis of the biomarker data, CA15–3 was discarded due to its low significance while a panel of 5 biomarkers was obtained as the best predictive model to discriminate p from healthy subjects. Results: 53 diferentially expressed proteins have been identified as potential breast cancer serum biomarkers after analysing 114 serum samples by 2DE Technology. A Protein Chip has been developed for the simultaneous detection of five serum biomarkers and three control proteins. After clinical validation with 200 p and healthy women, the sensitivity of the Protein Chip to detect breast cancer was 95% and its specificity was 27%. Conclusions: The high sensitivity of the Protein Chip suggests that it could be a valid tool to complement mammography (sensitivity < 80%) in breast cancer screening programs, specially when its sensitivity tends to decrease, as it happens in young women and dense breast cases. Larger clinical validation trials are being developed. This work is supported by INDAS BIOTECH.

No significant financial relationships to disclose.
Targeting prostate cancer progenitor cells with telomerase interference: A novel therapeutic strategy
Authors: Goldkorn A. , Xu T.
Published: August 2020

e22029

Background: We investigated whether telomerase, which is critical for benign stem cell activation, also plays a role in prostate cancer progenitor cells (PCPCs), which are thought to mediate therapy resistance and cancer progression, and we tested whether telomerase interference can effectively inhibit PCPC proliferation. Methods: A putative PCPC population was isolated from human prostatectomy specimens via collagen attachment and FACS selection for integrin α2β1 and CD44. PCPCs were characterized for gene expression (RT-PCR), clonogenicity (colony formation), invasiveness (matrigel chamber), and telomerase activity (qPCR-TRAP). PCPC telomerase interference was accomplished by lentiviral expression of 2 constructs: telomerase RNA with an altered template region (MT-Ter) and siRNA targeting wild-type telomerase RNA (anti-Ter siRNA). The effects of these constructs were assessed by measuring PCPC viability (MTS) and apoptosis (TUNEL assay). Results: An integrin α2β1+CD44+ putative PCPC population was isolated from 6 human prostate tumors. This population expressed high levels of “progenitor phenotype” genes (ABCG2, β-catenin, NANOG, Oct3/4) and low levels of “differentiated phenotype” genes (AR and PSA). PCPCs yielded >50 colonies per 1000 cells seeded on collagen after 3 weeks vs. none from FACS- cells, and matrigel chamber assay showed 10% of the PCPC population invading over 24 hours vs. none of the FACS- population. Most importantly, PCPCs possessed at least 20- fold greater telomerase activity than FACS- cells, and induction of telomerase interference in PCPCs via MT-hTer and anti- hTer siRNA expression elicited a brisk apoptotic response (TUNEL) by day 3 in >90% of cells, with concomitant near-complete growth inhibition (MTS). Conclusions: We have shown that human prostate tumors contain a subpopulation of prostate cancer progenitor cells (PCPCs) marked by an undifferentiated gene expression profile, vigorous clonogenicity and invasiveness, and high levels of telomerase activity that can be successfully exploited to neutralize these cells. Ongoing studies are investigating the in vivo effects of telomerase interference on PCPC tumorigenicity in mouse models.

No significant financial relationships to disclose.
Heterogeneous expression of prognostic and predictive antigens in primary and metastatic gastric cancer
Authors: Joka M. , Pietsch K. , Paulick S. , Issels R. , Jauch K. , Mayer B.
Published: August 2020

e22030

Background: Metastatic spread of cancer cells is a key event in tumor progression and in determining the prognosis of patients with malignant disease. This study evaluated the expression of prognostic and predictive molecules in primary and metastatic gastric cancer. Our objectives were to correlate the expression pattern with the clinicopathological features and patient survival and confirm the results using a coculture spheroid model. Methods: The clinicopathological features of 94 patients (57,4% male, 42,6% female, median age of 66,2 years) with gastric cancer were characterized using multivariate and univariate analysis. Further we compared the expression profile of biomarkers, namely EPCAM, CD44s, HLA-ABC and the associated β chain, HLA-DR, ICAM-1, LFA-3 and E-Cadherin in primary gastric tumors (n=94) and their synchronous metastases (regional lymph nodes n=32, liver n=14, peritoneum n=17) using immunoperoxidase staining. A coculture in vitro model, i.e. the homo- and heterotypic spheroid model were performed as a functional test system to confirm the microenvironmental impact on the biomarker expression level. Results: Strong HLA-ABC expression was found in both primary and metastatic tumors. High expression of HLA-ABC in liver metastases significantly correlated with metastatic disease (UICC TNM stage IV, p=0,026). Contrary, the detection of HLA-DR on the cancer cells correlated with the degree of the inflammatory infiltrate (CD45, p=0,019). With respect to CD44s, the prognostic marker was upregulated in the metastatic tumors independently of their localisation (p=0.009) compared to the primary lesions. E-cadherin and LFA-3 expression were preferentially increased in distant metastases, but not in locally advanced gastric tumors (liver: E-cadherin, p=0.001; liver and peritoneum: LFA-3, p=0.0067). E-cadherin expression was upregulated in the heterotypic spheroid model coculturing primary liver cells and N87 gastric cancer cells (80% E-cadherin positive N87 cells) compared to the homotypic spheroid model consisting of N87 cells alone (40% E-cadherin positive N87 cells). Conclusions: These data suggest the consideration of the metastatic protein profile for the selection of cancer patients in new molecular therapeutic strategies.

No significant financial relationships to disclose.
Correlation of plasma TIMP-1 levels and disease-free survival in primary colorectal cancer independent of serum CEA levels
Authors: Nielsen H. J. , Brünner N. , Christensen I. J.
Published: August 2020

e22040

Background: Introduction of independent prognostic markers may play a significant role in future treatment of early stage colorectal cancer (CRC). CEA is still the only recommended (ASCO and EGTM) serological marker in CRC. However, Tissue Inhibitor of Metallo Proteinases-1 (TIMP-1), which is a glycoprotein that acts as an inhibitor of most of the active matrix metalloproteinases, has previously been shown to carry independent prognostic information in patients with primary CRC. The purpose of the present study was to assess the combination of preoperative serum CEA and plasma TIMP-1as prognostic markers in patients undergoing resection for primary CRC. Methods: In the present prospective study serum and plasma samples were collected before surgery from 422 patients with primary CRC stage I-III. CEA was determined in serum by a commercial assay and TIMP-1 was determined in plasma using a thoroughly validated, in-house ELISA. Time to recurrence or death of CRC was registered and the association to serum CEA and plasma TIMP-1 levels were studied in a Cox multivariate model including age, gender, disease stage and tumor location. Hazard ratios and 95% confidence intervals (HR (95%CI)) for disease free survival (DFS) were calculated. Results: An event was recorded in 186 patients, 75 had local recurrence, 103 had a distant metastases (28 of these patients had both local recurrence and distant metastases) and 36 died from their cancer without a registered recurrence. Scoring CEA and TIMP-1 as continuous variables on a logarithmic scale (base 2), both serum CEA and plasma TIMP-1 were statistically significant in a multivariable analysis with HR=1.12 (1.03–1.21) and HR=1.51 (1.12–2.04), respectively. Additional calculations of low CEA plus low TIMP-1, high CEA plus low TIMP-1, low CEA plus high TIMP-1 and high CEA plus high TIMP-1 showed that high plasma TIMP-1 levels carried prominent information of poor prognosis independent of CEA. Conclusions: Preoperative serum CEA and plasma TIMP-1 levels were independent predictors of disease free survival for patients with primary CRC. Combination of the two proteins showed that TIMP-1 was a prominent predictor of poor DFS independent of CEA.

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Expression of CD24 as a predictor of prognosis of hepatocellular carcinoma after operation
Authors: Fan J. , Yang X. , Xu Y. , Shi Y. , Zhou J. , Qiu S.
Published: August 2020

e22043

Background: CD24 expression has previously been reported in hepatocellular carcinoma (HCC), although little is known about its prognostic significance. The aim of this study is to evaluate the relation of CD24 expression and its prognostic significance in HCC. Methods: CD24 expression in stepwise metastatic HCC cell lines and tumor tissues from 50 HCC patients was investigated by quantitative real-time reverse transcription-PCR and Western blot analyses. The role of CD24 was investigated by depletion CD24 expression in HCC cells through small-interfering RNA. Tumor tissue microarrays of 314 HCC patients who underwent resection between 1997 and 2000 were used to detect the expressions of CD24, β-catenin and PCNA expression. The prognostic significance was assessed using Kaplan-Meier survival estimates and log-rank tests. Results: CD24 was overexpressed in the high metastatic HCC cell line and in tumor tissues of recurrent patients. Depletion of CD24 caused a notable decrease in cell proliferation, migration and invasiveness in vitro. CD24 was confirmed as an independent predictor for overall survival (p<0.001) and relapse-free survival (p<0.001), regardless of recurrence time, AFP level, TNM stage and Edmondson stage. High expression of CD24 in HCC tissues was significantly associated cytoplasmic/nuclear accumulation of β-catenin (p=0.023), high tumor proliferate status (p=0.018) and diffused intrahepatic recurrence and distance metastasis (p=0.026). Adjuvant TACE after operation reduced the early recurrence (≤1 year) in CD24+ HCC patients (p=0.024), while there had no significant changes in CD24- patients (p=0.284). Conclusions: High expression levels of CD24 were related with high invasive and metastatic potential, high tumor proliferation status and activation of Wnt/β-catenin pathway. The expression of CD24 provides new prognostic information about HCC prognosis and targeted therapy to CD24+fraction in HCC may comprise a promising anti-recurrence strategy for HCC patients after surgery.

No significant financial relationships to disclose.
Comparative genomic and protein signatures and intratumoral treatment responses in patients with metastatic breast cancer (MBC) treated with paclitaxel (PTX) and 2-methoxyestradiol (2ME2)
Authors: Herold C. I. , Yang I. , Chi J. , Sidor C. , Parrillo L. , Liotcheva V. , Welch R. A. , Arnott J. , Dewhirst M. W. , Blackwell K. L.
Published: August 2020

e22049

Background: Tumors respond to both chemotherapy and radiation through a number of poorly understood survival mechanisms. These potential mechanisms include upregulation of anti-apoptotic and pro-angiogenic pathways, including those regulated by HIF-1α. Sequential MBC biopsies were used to examine 1) the effects of PTX on intratumoral HIF-1α mediated pathways; and 2) the ability of a HIF-1α inhibitor (2ME2) to modulate the tumor's HIF- 1α response to PTX. Methods: Key eligibility included pts with MBC, ECOG 0–2, unlimited prior therapies, and biopsiable tumors. Pts were treated on a 28-day schedule with weekly PTX (90 mg/m2 D1, D8, D15) and daily oral 2ME2 (1000, 1250,1500 or 2000 mg qid starting D8) and had 3 tumor biopsies: baseline (A); D8 post-PTX/pre-2ME2 (B); D22 post-PTX/post- 2ME2 (C). Serial biopsies were compared for genomic and single protein changes. Results: 20 pts (median age 52 yrs [31- 75]) were treated. 60% had ≥2 prior regimens for MBC, 35% had ≥3. No unexpected grade 3/4 toxicities were seen: neutropenia (n=6), anemia (2), hypophosphatemia (2), PE (1). The clinical benefit rate was 25% (4 PR, 1 SD). There were 13 pairs of tumor biopsies to compare points A/B and 10 to compare B/C. There were no consistent gene expression changes between A and B. Significant differences at C vs. B included changes in hypoxia-responsive genes (including CA9, HIF-2α) and upregulation of pro- angiogenic factors and hemoglobin transcripts. For the B/C comparison, 2 distinct groups emerged: the first (biopsy site liver) showed downregulation of gene expression programs driven by ER and the second (lymph node, breast) showed upregulation of endothelial cell- related genes. Conclusions: Combination therapy with PTX and 2ME2 is a well-tolerated and viable option for delaying disease progression for patients with heavily pretreated MBC. Significant gene expression changes before and after exposure to 2ME2 may reflect changes in tumor microcirculation consistent with the idea of vascular normalization. The potential significance of the differences in gene expression observed in the 2 distinct groups remains to be investigated. Supported by Komen Grant BCTR0504044 (MWD).

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The association of cancer and allergic symptoms among female adult participants aged ≥40 years in NHANES III
Authors: Chae Y. , Kim J. , Tester W.
Published: August 2020

e22060

Background: The contribution of inflammation to carcinogenesis has been reported. Allergic diseases are now recognized as a systemic inflammatory process. We investigated whether common allergic symptoms are associated with cancer risk. Methods: The Third National Health and Nutrition Examination Survey (NHANES III) is a stratified probability sample of the U.S. population collected during 1988–1994. The prevalence of cancer excluding skin cancer was obtained by personal medical interview. Allergic symptoms were categorized into three categories: no symptoms (NO), rhinitis/conjunctivitis without wheezing (RC), and wheezing (WZ). Other risk factors for cancer were defined by NHANES III questionnaire and results of physical examination. Multivariate logistic regression was used to obtain odds ratios of cancer according to the existence of allergic symptoms adjusted for other possible confounding variables considering complicated sampling methods and weights. Results: 4,558 female adults were selected out of 5076 female adults aged ≥40 years who participated in both interview and physical examination. Cancer was present in 7.41% (n=301). 36.3% (n=1,893) of subjects did not have any allergic symptoms (NO), 47.6% (n=1,979) showed RC, and 16.2% (n=726), WZ. The prevalence of cancer was 5.43% in NO, 7.63% in RC, and 11.23 in WZ (p=0.006). Unadjusted odds ratios of cancer were 1.44 (95% CI: 0.99–2.08, p=0.053) in RC and 2.20 (1.27–3.80, p=0.006) in WZ compared with NO. Odds ratios are 1.49 (1.00–2.22, p=0.048) in RC and 2.08 (1.11–3.89) in WZ adjusting for age, race, education, income, asthma, COPD, C-reactive protein, obesity, smoking, alcohol drinking, physical inactivity, and menopausal status. In subgroup analysis, adjusted odds ratios of breast cancer were 1.89 (1.04–3.42, p=0.037) in RC and 2.08 (0.90–4.78, p=0.084) in WZ, while other cancers showed no statistically significant associations. Conclusions: Common allergic symptoms, even symptoms of allergic rhinitis of conjunctivitis, may be associated with increased risk of cancer in female adults. It supports the hypothesis that systemic inflammation mediators may trigger or promote cancer development in all parts of the body. However, prospective studies are required to validate our findings.

No significant financial relationships to disclose.
Changes in phosphorylation and dephosphorylation status of cytoskeleton and their regulator proteins in CD34+ stem cells after G-CSF stimulation and in AML
Authors: Lannert H. , Lenze M. , Able T. , Park B. J. , Lenze A. , Meissner S. , Eckstein V. , Ho A. D. , Leicht S. , Franz T.
Published: August 2020

e22067

Background: The cytoskeleton is a cellular ‘scaffolding‘ or ‘skeleton‘ contained within the cytoplasm. It is a dynamic structure that maintains cell shape, enables cellular motion. ADF/cofilin is a family of actin-binding proteins which disassembles actin filaments. LIMK2 is phosphorylated and activated by ROCK, a downstream effector of Rho, and phosphorylates cofilin, inhibiting its actin-depolymerizing activity. Profilin binds to actin. At high concentrations, profilin prevents the polymerization of actin, whereas it enhances it at low concentrations. Cdk1 phosphorylates beta tubulin. In mitotic cells, phosphorylated tubulin is excluded from microtubules, being present in the soluble tubulin fraction. Stathmin/Op18 is a cytosolic phosphoprotein which regulates the dynamics of microtubules. The process of tumor proliferation and metastasis is characterized by high rates of mitosis and migration into distant tissues. In this study we investigated the expression of cytoskeleton proteins in native hematopoietic CD34+ stem cells from BM in comparison to mobilized peripheral blood stem cells (mPBSCs) from G-CSF stimulated donors as well as CD34+ cells from AML. Methods: An Auto-MACS (Miltenyi) and FACS Vantage SE cell sorter (Becton Dickinson) was used to process high enriched (>99%) CD34+ cells fractions from MNCs. Proteomics was performed with the Proteome Works System (BioRad). Protein identification was carried out by Q-TOF and ion trap mass spectrometer analyses. Phosphoproteins were detected with ProQ-Diamond stain and specific antibodies. Results: The comparative proteome analyses show that 1. actin, tubulin, vimentin are overexpressed and phosphorylated, 2. cofilin and profilin are unphosphorylated, and 3. Stathmin is overexpressed in G-CSF mobilized hematopoietic stem cells and in AML in his active ‘dephosphorylated‘ form. Conclusions: Highly enriched hematopoietic CD34+ cells are a prerequisite for the qualitative and quantitative phospho/proteome analyses. Our results show, that mobilized stem cells “in vivo” and AML cells increase cytoskeleton proteins expression and cause a complex phosphorylation status, which may explain the regulation of migration and metastasis.

No significant financial relationships to disclose.