bluuebunny/crossref_metadata_2025_split huggingface dataset:
BNIP3L (Nix) expression in colon cancer
Authors: Littlejohn J. E. , Jupiter D. , Cao X. , Zhang L. , Shabahang M. , Smythe W. R. 
Published: August 2020

e15097 Background: Microenvironmental adaptation to hypoxic conditions is critical for a cell to survive in a growing solid tumor. BNIP3L (Nix) mediates apoptosis during hypoxia in cancer cell lines, and Nix knockdown promotes tumor growth in-vivo through decreased apoptosis and increased proliferation, suggesting a means by which cells can adapt. Little is known specifically about Nix expression and its importance in human colon cancer. To gain insight into expression of this gene in colon tumors, the present study analyzed mRNA microarray data from 227 colon tumors and 22 normal colon tissue samples and queried differential expression of Nix. These results were compared to the protein levels present in human colon tumors. Methods: mRNA expression of 227 human colon tumors (made available by the Expression Project for Oncology (expO)) and 22 normal colon samples (retrieved from the Gene Expression Omnibus (GEO)) was analyzed. These samples were hybridized to the Affymetrix GeneChip Human Genome U133 Plus 2.0 Array, assaying 17,726 NCBI Entrez genes. Immunohistochemistry was performed on human tissue microarray CO701 (US Biomax, Inc.) containing 62 tumor samples. Results: Nix mRNA levels were shown to increase from normal to cancer (log-fold change of 0.961, Benjamini-Hochberg FDR adjusted p < 0.001). IHC demonstrated variable levels of Nix present in colon tumors: 38/62 (61.3%) of tumors stained positive for Nix while 24/62 (38.7%) were negative. Conclusions: We have shown that mRNA levels of Nix are upregulated in the transition from normal colon tissue to cancer but that protein levels in tumors demonstrate variable expression. This suggests that silencing of Nix occurs at various stages of tumorigenic progression and results in isolated populations of cells within a growing tumor that are uniquely resistant to apoptosis. Better understanding of Nix in the context of a growing colon tumor is needed and could lead to development of more successful therapeutics. No significant financial relationships to disclose.
Neoadjuvant chemoradiotherapy in rectal cancer patients (pt) with oxaliplatin (Ox) and capecitabine (Cp): Results of a phase II trial
Authors: Gasent Blesa J. , Alberola Candel V. , Juan O. , Provencio Pulla M. , Giner Marco V. , Gravalos C. , Fernandez I. , Llorca C. 
Published: August 2020

e15101 Background: Between April 2006 and May 2008, 27 rectal adenocarcinoma pt were included (cT3: 25 pt, T4: 2 pt, N0: 11 Pt, N+: 16 pt), stages II-III, RMN staged, 14 male and 13 female. Mehtod: Neoadjuvant treatment was: Ox: 50 mg/m2 weekly, oral Cp: 825 mg/m2 tid the days of the Rt, and a Rt of 50.4 Gy. 9 pt had a lower third tumor, 9 middle, 9 upper. Surgery was planned 6–8 weeks after treatment´s end. 4 adjuvant chemotherapy cycles with Xelox were planned. Results: 7 pt had pCR (26%), 2 pt progression disease 18 pt tumor downstaging(dwst). Percentages of dwst were: T 85%, N 37%. Sphincter preservation (sp) was 81.9%, for tumors of the lower third sp was 44.4%. Presurgical (prsrg) RMN did not predict the pathological result in 21 pt. Main side effects: Dermatitis G1 in 21 pt, and G2 in 4 pt. Diarrhea 12 pt G1, 11 pt G2, and 4 pt G3. Hand and foot G1 5 Pt and G2 4 pt. Paresthesias G1 10 pt, G2 7 pt. Leucopenia 6 pt G1. 4 Pt did not complete treatment because of toxicity. Median Rt dose was 49.7 Gy (47.5–50.4 Gy).At a mean follow up of 22.5 months (7–31) 4 pt presented metastatic disease (15% ), none in the pCR group. Mean pre-neoadjuvant (preneo) CEA was 6.8 ng/ml (2.1–17.0). There was difference statistically significant when compared preneo CEA vs prsrg CEA: 2.72 ng/ml inferior with the second outcome (p<0.001). Mean prsurg CEA was 4.1 (0.1–12.0). In the subgroup with pCR the mean prsrg CEA was 1.1 (0.5–1.5), and in non-pCR it was 5.1 (0.1–12.0). Comparing the prsrg CEA between pCR and the non-pCR subgroups, the mean difference was 4.0 ng/ml greater in the non pCR. This difference was statistically significant (p=0.002, 95% CI: 1.68–6.3).We found a nadir of <5ng/ml as significantly associated with pCR (p=0.036). Conclusions: Preoperative chemoradiotherapy with Ox and Cp, is safe and well tolerated. Offers an interesting ratio of pCR, and of tumor downstaging. Prsrg CEA level and CEA nadir should be studied as predictors of pCR. It is possible that with more patients, the significant nadir level could be lower. We consider this combination and the CEA nadir interesting to be included in further studies. No significant financial relationships to disclose.
Serum IGFBP3, IGF-I, and MMP7 changes in advanced colorectal cancer (ACRC) patients (pts) treated with anti-EGFR therapy: A GEMCAD study
Authors: Pineda E. , Pericay C. , García-Albéniz X. , Augé J. , Alonso V. , Escudero P. , Fernández-Martos C. , Gallego R. , Maurel J. 
Published: August 2020

e15109 Background: Insulin-like growth factor-I (IGF-I) is a potent mitotic and anti-apoptotic peptide, whereas IGF binding protein-3 (IGFBP3) seems to have pro-apoptotic effects. Matrix metalloproteinase-7 (MMP7), an enzyme with in vitro ability to degrade IGFBP3, has been shown to be a prognostic factor in ACRC. Methods: This is a prospective single cohort traslational study. Pts undergoing second/third line with irinotecan plus anti-EGFR therapy were eligible as cases. Patients with ACRC not undergoing therapy were eligible as controls. IGFBP3 and MMP7 were measured in serum with immunoassays at baseline and at 48h after treatment start. KRAS mutation status in codons 12/13 was determined by sequencing in 53 pts. The primary endpoint is to define the IGFBP3 and MMP7 variation under anti-EGFR therapy. IGFBP3 was used as a continuous variable and MMP7 was used to create two groups by its third quartile. Results: Eighty-five cases and 25 controls were recruited. No significant changes at 48h in IGF-I and IGFBP3 were found, but a significant decrease in MMP7 from 10.8 (95%IC 8.3–13.3) to 8.4 ng/ml (95%IC 6–10.9) was observed in cases (p<0.001) in contrast with controls, where no changes were found. Splitting the sample by the third quartile of MMP7 interesting changes in IGFBP3 variations were found. In the group with low levels of MMP7, IGFBP3 increases from 1,859 to 1,959 ng/ml (p=0.043) 48h after treatment initiation; on the contrary, in the group with high levels of MMP7, IGFBP3 decreases from 1,811 to 1,757 ng/ml (p=0.741). We found no association with IGFBP3 and neither response rate, time to progression nor overall survival. This latter analysis was also done only in pts with wild-type KRAS, without any change in the results. Conclusions: In pts with ACRC treated with anti-EGFR therapy, serum levels of IGFBP3 variations depend on basal MMP7 levels. IGFBP3 failed to be a predictive/prognostic factor in our sample although the limited number of KRAS pts analyzed can influence our results. [Table: see text] No significant financial relationships to disclose.
Phase I study of RAD001 (everolimus), cetuximab, and irinotecan as second-line therapy in metastatic colorectal cancer (mCRC)
Authors: Sharma S. , Reid T. , Hoosen S. , Garrett C. , Beck J. , Davidson S. , MacKenzie M. , Brandt U. , Hecht J. 
Published: August 2020

e15115 Background: The PI3K/AKT/mTOR pathway is frequently dysregulated in colorectal cancer (Cancer Res 2005;65:11227). In a phase I study in patients with advanced solid tumors, everolimus an oral mTOR inhibitor demonstrated clinical benefit including a partial response in pts with colorectal cancer (J Clin Oncol 2008;26:1603–10; J Clin Oncol 2008; 26:1588–95). Methods: This open-label, multicenter phase I study uses a Bayesian logistic model to identify feasible doses of everolimus + irinotecan + cetuximab. Adult pts with mCRC progressing despite prior 5-FU/oxaliplatin (FOLFOX) or capecitabine/oxaliplatin (XELOX) plus bevacizumab (if standard practice) were treated using a sequential dose escalation scheme (Table). Dose decisions were driven by the probability of dose-limiting toxicity (DLT) in the first 2 cycles. Dose level decisions were based on maximizing the probability that end-of-cycle-2 DLT rate would be within the targeted toxicity interval (20% to <35%) and minimizing the risk of over-dosing (< 5% risk of unacceptable toxicity and < 25% risk of excessive/unacceptable toxicity). Results: 18 pts were treated from April ‘07 to August ‘08, 5 pts at dose level A1 and 13 pts at dose level B1. Two DLTs (G3 rash on cycle 2 day 1 lasting > 7 days and G3 mucositis on cycle 1 day 14 lasting > 7 days, 1 pt each) were reported in 4 evaluable pts at dose level A1. No DLTs were reported in 7 evaluable patients at dose level B1. Conclusions: At dose level B1 everolimus in combination with irinotecan and cetuximab was generally well tolerated. The study was stopped due to changes in clinical practice based on emerging data indicating that cetuximab has limited efficacy in mCRC patients with KRAS mutations and that efficacy data favors daily RAD001 over weekly dosing. Patients in this study were treated with cetuximab irrespective of KRAS status. [Table: see text] [Table: see text]
Phase II study of capecitabine plus oxaliplatin for the first-line treatment of patients with metastatic colorectal carcinoma
Authors: Xu none R. , Li Y. , Luo H. , Wang F. 
Published: August 2020

e15125 Background: The purpose of this study was to evaluate the safety and efficacy of the capecitabine-oxaliplatine combination (XELOX) in Chinese patients with metastatic colorectal carcinoma (mCRC). Furthermore, we aimed to explore whether a maintenance therapy with oral capecitabine in patients responding to XELOX is able to maintain the response and improve the duration of disease control (DDC). Methods: Patients with mCRC were treated with a 3-weekly regimen of oxaliplatin at a dose of 130 mg/m2 intravenously on Day 1 plus capecitabine 1000 mg/m2 orally twice daily from Days 2 to 15. Patients who did not progress after finished the XELOX therapy were choice to stop or receive oral capecitabine until disease progression or unacceptable toxicity. Results: 124 patients received a total of 637 cycles (median, 6) of treatment. Responses rate was 49.1%. Median overall and median progression-free survival was 20.0 months and 8.0 months, respectively. Main grade 3–4 drug-related toxicities included neutrapenia (5.6%), nausea/vomiting (4%), thrombocytopenia (2.4%), and hand-foot syndrome (2.4%). 23 of 101 patients responding to XELOX received oral capecitabine as maintenance therapy.The median DDC was 8 months for patients in the group of not using maintenance therapy, versus 12 months in the group of using capecitabine as maintenance therapy. Conclusions: XELOX is a highly effective first-line treatment for mCRC and provides a more convenient regimen, likely to be preferred by both patients and healthcare providers. Furthermore, these results support the feasibility of maintaining good response and improving DDC with oral Capecitabine after combination chemotherapy in mCRC. No significant financial relationships to disclose.
Positive expression and correlation of chemokine receptor CXCR4 with nodal metastasis and prognosis in colorectal cancer
Authors: Iqbal K. 
Published: August 2020

e15128 Background: Colorectal cancer is one of the leading causes of cancer related deaths,with recurrence and metastasis as the primary reasons for mortality. New evidence hasimplicated Chemokines as the likely cause. We studied the positive expression of CXCR4 chemokine receptors in colorectal carcinoma and investigated its correlations to clinicpathologic characteristics and prognosis. Methods: Tumor tissue specimens of patients with colorectalcarcinoma (n = 67) who underwent surgery from January 2003 to December 2004 at the Department of Surgery, Tongji Hospital were collected. CXCR4 expression levels and tumor micro vessel density were evaluated by immunohistochemistry. Specimens were immunostained using formalin-fixed, paraffin-embedded tissues. The correlation between the CXCR4 expression and clinicopathological factors was evaluated Results: In 67 cancer tissue specimens, CXCR4 was positively expressed in 38 cases; positive rate being 56.7%. Positive expression of CXCR4 is associated with an increase incidence of nodal involvement, higher clinic stage, higher tumor micro vessel density and a lower 3-year disease free survival rate as compared to those with negative CXCR4 expression (P<0.05). Conclusions: Positive CXCR4 expression and high tumor micro vessel density are associated with poor prognosis and could be a potential predictive factor for recurrence or metastasis of colorectal cancer patients. So CXCR4 may be a potential target for specific therapeutic interventions in the future. No significant financial relationships to disclose.
A phase II clinical trial utilizing maximum medical and surgical cytoredutive treatments for patients with metastatic colorectal cancer to the liver
Authors: Glisson S. D. , LaRocca R. V. , Hargis J. B. , Cervera A. , Goldsmith G. , Cornell B. , Repishti D. D. , Sunderland J. E. 
Published: August 2020

e15130 Background: The median overall survival (‘OS‘) for patients with mCRC treated with chemotherapy is about 20.4 months. Combination chemotherapy with surgical cytoreduction for patients with liver metastases are evaluated in a phase II clinical trial. Methods: Patients with newly diagnosed mCRC to the liver or recurrent CRC after 5FU failure were consented to receive further chemotherapy with at least irinotecan-based chemotherapy, oxaliplatin-based chemotherapy, and with the intention to treat the liver metastases with either RFA and/or liver resection between chemotherapy regimens whenever possible. Bevacizamab and cetuximab were considered options for treatment after their respective FDA approvals. Chemotherapy was given until there was treatment failure. The primary endpoint was OS. Results: Between 2001 and 2004 thirty-seven patients aged 41 to 79 were consented. One remained alive by December 2008. Only patients with an ECOG performance status of 0–1 were consented. Twenty had been treated with 5FU for a stage III CRC befored developing mCRC. All patients received irinotecan in the form of FOLFIRI, IFL, or as a single agent. Thirty-six also received oxaliplatin in the form of either FOLFOX4 or 6. Twenty-two patients received cetuximab as a single agent. Some regimens were augmented with bevacizumab. Fourteen patients could not undergo resection or RFA because of performance status or progression. Three required radiation to the CNS or distant bone. There were eleven patients who underwent RFA of at least one liver metastasis. There were ten patients who underwent liver resection. One patient underwent both RFA and liver resection at two different times. Another patient underwent RFA, adrenalectomy and wedge resection of the lung at three different times. He remained alive at 78 months at the time of submission. Median OS was 34.5+ months at the time of submission. Patient survival ranged from 15 to 86 months. There were no deaths associated with any surgical intervention. Conclusions: OS was improved in mCRC patients or recurrent CRC patients who had potentially ablatable or resectable liver lesions at the time of their diagnosis and who were treated with available aggressive medical and surgical therapies. [Table: see text]
A review of the outcomes of patients with anal cancer enrolled in the Hurley Cancer Registry: 1987-2004
Authors: Subramonia Iyer S. , Akl A. 
Published: August 2020

e15131 Background: This paper describes the outcomes of patients with anal cancer enrolled in the Hurley Cancer Registry. Methods: Retrospective registry and chart review study. The Hurley cancer registry was searched using diagnosis codes for anal cancer. The records retrieved, were reviewed for demographic and pathologic details,cancer recurrence, and vital status at last follow up. Relative survival was calculated for the patient cohort. Results: Over a period of 18 years (1987 - 2004), there were 36 patients enrolled in the registry, with a diagnosis of anal cancer. There were 18 males and 18 females. Mean age at diagnosis was 59.3 (SD 17.6) years for males, and 64.6 (SD 13.8) years for females. Squamous cell cancers were the most common: 27 / 36 (75%). The median survival of these 36 patients was 6 years. The median disease free survival was 5.3 years. Five patients (14%) developed recurrent disease during follow up, after a median of 1.8 years (range: 0.67- 4.2 years). Four of these patients had local recurrence only. One patient had local, regional recurrence with distant metastases. Three of the five (60%) recurrent cancers were associated with HIV infection. For all patients without recurrence, the median survival is 7.1 years. Relative survival is the observed survival adjusted for expected mortality. The expected survival probabilities for 3-yr and 5-yr intervals were calculated using the age, sex and race- matched survivorship information U.S. population life tables for 1989–91 and 1999–2001. Cumulative survival functions for the cohort were derived for the time points of 3-yrs and 5-yrs after diagnosis. The relative survival for the cohort was 84.6% at 3 years and 79.8% at the end of five years of follow up. These results appear superior when compared to the overall 5-year relative survival rate for 1996–2004 from 17 SEER geographic areas, which was 66.5%. Conclusions: Among patients in the Hurley Cancer Registry, 1. Squamous cell carcinoma is the commonest (75%) anal cancer. 2. The risk of recurrence of anal cancer was 14% over 6-years, and 80% of recurrence was localised to the anal canal. 3. The relative survival for the cohort was 79.8% at the end of five years of follow up. This was 78.9% for the subgroup of patients without recurrence, and 86.1% for the subgroup with recurrent disease. No significant financial relationships to disclose.
Polymorphism detection of K-Ras mutations using high-resolution melting analysis in Mexican patients with metastatic colorectal cancer (mCRC)
Authors: Astudillo H. , Sanchez-Guillen J. , Romero-Garcia P. , Bastarrachea-ortiz J. , Morgan-Villela G. , Salazar J. M. , Vazquez-Rivera V. M. , Ruiz-Calzada H. , Cortes-Esteban P. 
Published: August 2020

e15135 Background: Metastatic carcinoma of the colorectum remains a major problem. Nowadays the mutational polymorphism detection of K-ras gene is useful for patients with diagnosis of mCRC especially when an anti-EGFR biological therapy is considered to be used. The purpose of this study was to analyze and establish a molecular method to detect the mutational polymorphism of K-Ras gene in paraffin-embedded biopsies from Mexican patients with mCRC. Methods: The presence and polymorphism of K-ras gene mutations were analyzed in paraffin-embedded biopsies from 156 patients using a real time PCR technique with target specific oligomer competitor shifting the PCR amplification towards the mutated target, thus yielding an enriched PCR product containing variations. Results: K-ras mutations were detected in 89 of 156 patients (59%). There was not evaluated a relationship between the presence of a K-ras mutations and clinicopathological features. 39 of the 89 (42.85%) biopsies with a positive K- ras mutation had a 12G mutation polymorphism, 11 of the 89 (12.08%) biopsies had a 12D mutation polymorphism and 10 of the 89 (10.98%) biopsies had a 12S mutation polymorphism. Of the 64 biopsies without K-ras mutation (wild type), none clinicopathological correlation was determine in this group. The rate of the K-ras mutation was higher than that of the K-ras mutation negative group (wild type). Conclusions: This study demonstrates that the determination of mutational polymorphism of k-ras gene is possible and could be implemented as a predictor response in patients with mCRC to benefit from antibody based anti-EGFR therapies. No significant financial relationships to disclose.
Safety, efficacy, and time to clinical response with bevacizumab plus FOLFIRI regimen in metastatic colorectal cancer
Authors: Tomao S. , Spinelli G. , Rossi L. , Pasciuti G. , Arcangeli G. , D’Aprile M. , Veltri E. , Baiano G. 
Published: August 2020

e15138 Background: Bevacizumab (BEV) has shown clinical activity in metastatic colorectal cancer patients (mCRC)and randomised phase III trials have demonstrated that this agent significantly improves overall and/or progression-free survival when added to first-line irinotecan based chemotherapy (CT) regimens. We evaluated the efficacy and safety of BEV plus FOLFIRI (irinotecan, 5- fluorouracil, and leucovorin) as first line treatment in 27 consecutive metastatic colorectal cancer cases, with the primary end point to calculate the median time to clinical response with this chemotherapeutic schedule. Methods: Between October 2007 and January 2008 we collected the data on 27 patients with mCRC treated with first line chemotherapy with BEV plus FOLFIRI. Elegibility criteria had to be: mCRC; no prior CT for metastatic disease; ECOG PS 0/1, adequate organ function; no CNS metastases. The treatment consisted of a minimum of six cycles of irinotecan plus infusional 5-FU/LV according to the classical FOLFIRI schedule; BEV (5mg/kg) was given on day 1 with CT and then every 2 weeks until disease progression. Safety and response were assessed at the time of first CT and every 4 weeks thereafter. Results: 27 pts were evaluable (male 18; median age 61 years (range 45–77), ECOG PS 0: 52%, PS 1: 48%. The sites of metastases were: liver (15 pts), lung (5 pts), liver and lung (5 pts), peritoneal wall (2 pts).Median follow-up was 18 weeks. Two patients had complete response(CR) and 13 pts partial response (PR), with an overall response rate of 57.7%. Five patients had stable disease and 6 patients showed progressive disease. A clinical benefit was demonstrated in 77 % of pts. We observed a median time to clinical response of 11 weeks, evaluated with tumor markers and with CT/NMR/US examinations. A grade 3 or 4 neutropenia was detected in 39% of pts and grade 2 or 3 hypertension in 9%. We did’nt observe cases of thrombosis, bleeding and gastrointestinal perforation, sometimes related to the use of BEV. Conclusions: In this little experience the efficacy and safety of BEV associated with FOLFIRI schedule, a first line therapy in mCRC,is consistent with results from other previous studies, showing moreover a short time to clinical response with this association. No significant financial relationships to disclose.