tbuckley/cabot-search huggingface dataset:
Immunihistochemical detection of galNAc-T6 to predict survival in patients with colon cancer.
Authors: Luis Ubillos, Mariela Rondan, Edgardo Berriel, Daniel Mazal, Enrique Barrios, Nora Berois, Eduardo Osinaga
Journal: Journal of Clinical Oncology (2013)

e14682 Background: Alterations in the O-glycosylation is one of the most common changes during colon carcinogenesis, which leads to the expression of short O-glycan antigens (Tn, sialyl-Tn, Tk, and core 6). These structures are associated with malignant behavior being actively investigated as targets for immunotherapy. The enzymes of GalNAc-T family regulate the initial step in mucins O-glycosylation and could be responsible for the altered glycosylation observed in cancer. The aim of this work was to evaluate the expression of GalNAc-T6 in colon cancer, and to determine its role as prognostic marker. Methods: We evaluated GalNAc-T6 expression in colon cell lines by immunocytochemistry, and in colon cancer tissue samples by immunohistochemistry using the monoclonal antibody T6.3 developed by us (Berois et al. J Histochem Cytochem. 2006). We analyzed 103 colon cancer samples and 10 normal colon tissues. Results: We found that GalNAc-T6 (usually expressed in normal placenta, trachea, pancreas and brain) is detected in colon cancer cell lines. GalNAc-T6 was also detected by immunohistochemistry in 50.5% of samples with cancer and no expression was found in normal colon tissue. The staining pattern was predominantly cytoplasmic. Multivariate analysis showed that GalNAc-T6 expression is an independent prognostic marker predicting improved survival in patients with positive tumors (p 0.014). Conclusions: GalNAc-T6 could be a new independent prognostic marker to predict better outcome in colon cancer patients.
EFFECTS OF ACR GRADE 2R REJECTION TREATMENT ON MYOCARDIAL T1 AND T2 DURING YEAR ONE POST HEART TRANSPLANTATION
Authors: Muhannad Abbasi, Roberto Sarnari, Julie Blaisdell, Kambiz Ghafourian, Jane Wilcox, Sadiya Khan, Esther E. Vorovich, Jonathan Rich, Allen S. Anderson, Clyde W. Yancy, Michael Markl, James C. Carr
Journal: Journal of the American College of Cardiology (2020)
Phylogenetically informative mutations in genes implicated in antibiotic resistance in Mycobacterium tuberculosis complex
Authors: Matthias Merker, Thomas A. Kohl, Ivan Barilar, Sönke Andres, Philip W. Fowler, Erja Chryssanthou, Kristian Ängeby, Pontus Jureen, Danesh Moradigaravand, Julian Parkhill, Sharon J. Peacock, Thomas Schön, Florian P. Maurer, Timothy Walker, Claudio Köser, Stefan Niemann
Journal: Genome Medicine (2020)

A comprehensive understanding of the pre-existing genetic variation in genes associated with antibiotic resistance in the Mycobacterium tuberculosis complex (MTBC) is needed to accurately interpret whole-genome sequencing data for genotypic drug susceptibility testing (DST).
OUTCOMES OF TRANSCATHETER MITRAL VALVE REPAIR IN PATIENTS WITH SECONDARY MITRAL REGURGITATION ACCORDING TO THE SEVERITY OF LEFT VENTRICULAR DYSFUNCTION: THE COAPT TRIAL
Authors: Stamatios Lerakis, Annapoorna Subhash Kini, Saibal Kar, None Kar, Scott Lim, Jacob M. Mishell, Brian Whisenant, Michael Rinaldi, Samir R. Kapadia, Vivek Rajagopal, Ian Joseph Sarembock, Andreas Brieke, Neil J. Weissman, Federico M. Asch, Paul A. Grayburn, Gilbert Tang, Aaron Crowley, Samin K. Sharma, JoAnn Lindenfeld, William Abraham, Michael Mack, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2020)
Prognostic significance of PI3K pathway (PI3Kp) dysregulation in metastatic breast cancer (MBC) patients (pts).
Authors: Alejandro Navarro, Mafalda Oliveira, Leticia De Mattos-Arruda, Gessamí Sánchez-Ollé, Meritxell Bellet, Judith Balmaña, Patricia Gómez-Pardo, Jose Manuel Perez-Garcia, Eva Muñoz-Couselo, Maria Vidal, Vanesa Ortega, Rodrigo Dienstmann, Claudia Aura, Javier Hernandez-Losa, Jordi Rodon, Santiago Ramon y Cajal, José Baselga, Josep Tabernero, Javier Cortes, Cristina Saura
Journal: Journal of Clinical Oncology (2012)

566 Background: PI3Kp dysregulation represents a potential target for therapies that are currently being tested in clinical trials. This observational retrospective study aims to evaluate the prognostic implications of PI3Kp dysregulation in MBC. Methods: MBC pts with PI3Kp status assessment from Sep09 to Sep11 were reviewed. PIK3CA mutation status analyzed in paraffin-embedded tissue by DxS PI3K Mutation Test Kit or Sequenom MassARRAY. PTEN status determined by IHC. PI3Kp status: (a) No dysregulation: PIK3CA wt and PTEN normal; (b) PI3Kp dysregulation: PIK3CA mutation (PIK3CAmut) or PTEN low (HScore≤50). Results: 232 MBC pts screened, median age 49.8 (22.9-83.1) and median MBC lines 4 (1-15). Distribution: HR+/HER2- 99 (43%), HER2+ 52 (22%), triple negative 35 (15%), unclassified 46 (20%). Sites of metastasis: visceral 173 (75%), only skin 10 (4%), only bone 49 (21%). PIK3CA status assessed in 174 pts, 53 (22.8%) bearing a mutation (21 exon9, 32 exon20). PTEN status assessed in 229 pts, PTEN low 61 (26.6%). PI3Kp dysregulation in 103/185 pts (55.6%). Time to progression to first line MBC treatment (TTP) and overall survival after MBC diagnosis (OS) are shown. Disease free survival (DFS) and distant-disease free survival (DDFS) in pts initially diagnosed with early breast cancer (n=193) has also been calculated. Conclusions: These results suggest that PI3Kp dysregulation, either by PIK3CA mutation or PTEN low, does not seem to have impact on disease recurrence, response to first line MBC treatment or overall MBC survival.[Table: see text]
The importance of constraints on constraints
Authors: Christopher J. Bates, Chris R. Sims, Robert A. Jacobs
Journal: Behavioral and Brain Sciences (2020)

Abstract The “resource-rational” approach is ambitious and worthwhile. A shortcoming of the proposed approach is that it fails to constrain what counts as a constraint. As a result, constraints used in different cognitive domains often have nothing in common. We describe an alternative framework that satisfies many of the desiderata of the resource-rational approach, but in a more disciplined manner.
Bowen’s disease
Authors: Padma Mohandas, Martyn Lowden, Sandeep Varma
Journal: BMJ (2020)

### What you need to know

A 68 year old woman with skin type 1 presents with an 18 month history of a well circumscribed 10 mm erythematous scaly patch over her left shin. Since retirement, she has lived in Spain for part of the year and has now returned to the UK, worried that the patch has increased in size. 

In Bowen’s disease the full thickness of the epidermis is dysplastic with atypical keratinocytes, but these have not yet breached the basement membrane to become a squamous cell carcinoma. Reflecting this, Bowen’s disease is also commonly known as squamous cell carcinoma in situ and as intraepidermal or intraepithelial carcinoma. Historically, progression of Bowen’s disease to squamous cell carcinoma was believed to be 3-5%.1 However, a 2017 study suggested that it may be much higher, with 16.3% of 566 cases of biopsy-proven Bowen’s disease found to have squamous cell carcinoma when treated surgically.2

This article outlines the assessment and management of Bowen’s disease in a primary care setting. Rarer variants of Bowen’s disease may present as pigmented plaques, nail dystrophy or discolouration, or patches and plaques in the genitalia, but this article focuses on the common presentation likely to be seen in primary care.

### How this article was made

We conducted a literature review of articles and guidelines, reviewed dermatology textbooks, and sought expert advice from general practitioners and consultant dermatologists regarding Bowen’s disease.

The classic presentation of Bowen’s disease is of an asymptomatic, well circumscribed, solitary, erythematous patch or plaque on a sun-exposed site (typically head, neck, or limb), usually 10-15 mm in diameter that has been slowly growing (fig 1 …
THE ROLE OF LOCAL ENDOTHELIAL SHEAR STRESS (ESS) IN THE DEVELOPMENT OF CORONARY ARTERY DISEASE IN CARDIAC TRANSPLANT PATIENTS: POSSIBLE MAGNIFICATION OF ESS PATHOBIOLOGIC EFFECT RELATED TO IMMUNOLOGIC FACTORS OF REJECTION
Authors: Zhongyue Pu, Ahmet U. Coskun, Gerasimos Siasos, Jaskanwal Deep Singh Sara, Charles Maynard, Nicholas V. Cefalo, Shigeo Gogo, Toya Takumi, Sudhir Kushwaha, Michelle A. Cormier, Marina Zaromytidou, Anubodh S. Varshney, Kevin J. Croce, Amir Lerman, Peter Howard Stone
Journal: Journal of the American College of Cardiology (2020)
ENDOTHELIAL PROGENITOR CELLS &amp; VASCULAR ENDOTHELIAL GROWTH FACTOR A IN PATIENTS WITH TYPE 2 DIABETES MELLITUS AFTER PERCUTANEOUS VASCULAR INTERVENTIONS
Authors: Raisa Kosharnaya, Marina Michurova, Ilya Giverts, Victor Kalashnikov, Alexander Zakharov
Journal: Journal of the American College of Cardiology (2020)
Cost of febrile neutropenia management in cancer patients in Spain
Authors: J. I. Mayordomo, A. López, N. Viñolas, J. Castellanos, S. Pernas, J. D. Alonso, A. Frau, M. Layola, J. A. Gasquet, J. Sánchez
Journal: Journal of Clinical Oncology (2006)

6089 Background: Febrile neutropenia (FN), a dose-limiting event for many myelosuppressive chemotherapy (CT) regimens, often causes subsequent CT dose delays (DD) and reductions (DR), lengthens hospital stay and increases monitoring, diagnostic and treatment costs. No studies are known to date on economic costs of FN in common clinical practice in Spain. Methods: This is a multicentre, retrospective, observational chart review of adult patients with breast cancer, lung cancer or non-Hodgkin’s lymphoma (NHL) who suffered from at least one FN episode related to cytotoxic CT from 16 Spanish hospitals. Resource use and subsequent costs including days of hospitalization, number of RBC transfusions, number and type of complementary tests, use of colony-stimulating factors (CSF), antibiotics and other drugs to manage FN were assessed. Potential impact of FN on planned CT dose and/or schedule was also analysed. P-value was obtained by one-way ANOVA using the Bonferroni correction. Results: A total of 194 medical charts including 238 documented FN episodes were reviewed. Women, 59.8%; age &gt; 60 yrs, 49.5%; breast cancer, 43% (83% treated with taxane or anthracycline-based CT); lung cancer, 22% (95.5% treated with platinum-based CT); NHL, 35% (58.2% treated with CHOP-like CT). Hospitalization due to FN lasted a median of 7 days. During the episode, 32.3% of pts needed 1 or more RBC transfusions, 97.9% required a blood test and 87% a blood culture. CSFs were used in 67.6% of pts. All pts were treated with antibiotics and 78.2% with other drugs. 58.4% of FN episodes had an impact on planned CT dose and/or schedule: DR was observed in 34.9% of cases, DD in 28% and CT withdrawal in 14.7%. Conclusions: Main drivers of cost of FN are hospitalization and antibiotic treatment. FN is more costly in NHL pts than breast or lung pts (statistically significant in lung pts). FN episodes have a relevant impact on planned CT dose and/or schedule. In each row statistically significant differences ( p&lt;0.05) were obtained between values with the same letter. [Table: see text] [Table: see text]
A framework for transcriptome-wide association studies in breast cancer in diverse study populations
Authors: Arjun Bhattacharya, Montserrat García-Closas, Andrew F. Olshan, Charles M. Perou, Melissa A. Troester, Michael I. Love
Journal: Genome biology (2020)

The relationship between germline genetic variation and breast cancer survival is largely unknown, especially in understudied minority populations who often have poorer survival. Genome-wide association studies (GWAS) have interrogated breast cancer survival but often are underpowered due to subtype heterogeneity and clinical covariates and detect loci in non-coding regions that are difficult to interpret. Transcriptome-wide association studies (TWAS) show increased power in detecting functionally relevant loci by leveraging expression quantitative trait loci (eQTLs) from external reference panels in relevant tissues. However, ancestry- or race-specific reference panels may be needed to draw correct inference in ancestrally diverse cohorts. Such panels for breast cancer are lacking.
RELATION BETWEEN CARDIO-ANKLE VASCULAR INDEX AND CORONARY ARTERY CALCIFICATION OR STENOSIS IN METABOLIC SYNDROME SUBJECTS
Authors: Thosaphol Limpijankit, Suttipong Jongjirasiri, Khanchit Likittanasombat, Krissada Meemook, Nattawut Unwanatham, Ammarin Thakkinstian, Piyamitr Sritara, Jiraporn Laothamatas
Journal: Journal of the American College of Cardiology (2020)
ASSOCIATION BETWEEN CARDIAC VARIABLES AND COGNITIVE FUNCTION IN MIDDLE-AGED ADULTS: ANALYSIS FROM THE DALLAS HEART STUDY-2
Authors: Richard Chia, Colby Ayers, Heidi Rosetti, Ambarish Pandey, Jarett D. Berry, Julia Kozlitina, Mark H. Drazner, Sonia Garg, Ronald Peshock, James A. de Lemos, Rong Zhang, Wanpen Vongpatanasin
Journal: Journal of the American College of Cardiology (2020)
The autologous hemopoietic stem cell transplantation in adult patients with lymphoma: Turkish Bone Marrow Transplantation Registry Results
Authors: T. Turkish
Journal: Journal of Clinical Oncology (2006)

17517 Background: Turkish bone marrow transplantation registry (TBMTR) was established in 1995. Since 1992, data of adult lymphoma patients from fifteen transplant centers were collected and analyzed by TBMTR. Methods: A total of 437 adult lymphoma patients (185 Hodgkin’s and 252 non-Hodgkin’s lymphoma) undergoing autologous hemopoietic stem cell transplantation (HSCT) were registered by TBMTR from 1992 to 2002. Results: Peripheral blood was used in 94% of the transplantations as a source of stem cells. Non-TBI conditioning regimens were administered in 88% of the cases. The 100-day transplant related mortality was 11% in relapsed and in primary refractory Hodgkin’s lymphoma patients; while transplant-related mortality (TRM) was found to be 9% and 30% in non-Hodgkin’s lymphoma patients in first remission and in primary refractory cases, respectively. Infection was the most common cause of TRM. Overall (long-term) survival rates were 50% and 49% in relapsed cases and primary refractory cases with Hodgkin’s lymphoma, respectively; while in non-Hodgkin’s lymphoma patients the survival rates were 65% in cases in first remission, 50% in sensitive relapse, 0% in resistant relapse and 24% in primary refractory cases. Conclusions: In conclusion, TBMTR results are comparable to EBMT and IBMTR results. Therefore, autologous HSCT may provide long-term survival in patients with Hodgkin’s lymphoma as well as in patients with non-Hodgkin lymphoma in first remission and in sensitive relapse. Contributing authors and centers: F. Arpaci 1 , S. Ataergin 1 , G. Gurman 2 , S. Cagirgan 3 , M. Arat 2 , A. Ozet 1 , M. Ayli 4 , M. Ozcan 2 , A. Unal 5 , T. Soysal 6 , Y. Koc 7 , A. Buyukcelik 8 , A. Ozturk 9 , E. Ovali 10 , H. Goker 11 , B. Sahin 12 , S. Kalayoglu Besisik 13 , M. Bayik 14 , Z. Bolaman 15 , S. Bavbek 16 , M. Turan 1 1 GATA; 2 Ankara University Hematology; 3 Ege University; 4 Numune Hospital, Ankara; 5 Erciyes University; 6 Cerrahpasa University; 7 Hacettepe University Institute of Oncology; 8 Ankara University Medical Oncology; 9 GATA Haydarpasa; 10 Karadeniz University; 11 Hacettepe University; 12 Cukurova University; 13 Istanbul University Hematology; 14 Marmara University; 15 A.Menderes University; 16 Istanbul University Institute of Oncology. No significant financial relationships to disclose.
GPD1 Enhances the Anticancer Effects of Metformin by Synergistically Increasing Total Cellular Glycerol-3-Phosphate
Authors: Jianjiang Xie, Jianheng Ye, Zhiduan Cai, Yong Luo, Xuejin Zhu, Yulin Deng, Yuanfa Feng, Yingke Liang, Ren Liu, Zhaodong Han, Yuxiang Liang, Yu Zheng, Rujun Mo, Yangjia Zhuo, Yongding Wu, Funeng Jiang, Jianguo Zhu, Chin-Lee Wu, Weide Zhong
Journal: Cancer Research (2020)

Abstract Metformin is an oral drug widely used for the treatment of type 2 diabetes mellitus. Numerous studies have demonstrated the value of metformin in cancer treatment. However, for metformin to elicit effects on cancer often requires a high dosage, and any underlying mechanism for how to improve its inhibitory effects remains unknown. Here, we found that low mRNA expression of glycerol-3-phosphate dehydrogenase 1 (GPD1) may predict a poor response to metformin treatment in 15 cancer cell lines. In vitro and in vivo, metformin treatment alone significantly suppressed cancer cell proliferation, a phenotype enhanced by GPD1 overexpression. Total cellular glycerol-3-phosphate concentration was significantly increased by the combination of GPD1 overexpression and metformin treatment, which suppressed cancer growth via inhibition of mitochondrial function. Eventually, increased reactive oxygen species and mitochondrial structural damage was observed in GPD1-overexpressing cell lines treated with metformin, which may contribute to cell death. In summary, this study demonstrates that GPD1 overexpression enhances the anticancer activity of metformin and that patients with increased GPD1 expression in tumor cells may respond better to metformin therapy. Significance: GPD1 overexpression enhances the anticancer effect of metformin through synergistic inhibition of mitochondrial function, thereby providing new insight into metformin-mediated cancer therapy.
Widening participation: moving from diversity to inclusion
Authors: Molly V Fyfe, Sonia Kumar, Arti Maini, Jo Horsburgh, Bethany Golding
Journal: BMJ (2020)

The BMJ ’s investigation describes the ongoing racial discrimination that ethnic minority medical students face and the lack of meaningful response from medical schools.1 We must consider these serious matters in light of ongoing initiatives to widen participation, aimed at increasing the number of students from under-represented ethnic minorities in …
Triple artemisinin-based combination therapies versus artemisinin-based combination therapies for uncomplicated Plasmodium falciparum malaria: a multicentre, open-label, randomised clinical trial
Authors: Rob W van der Pluijm, Rupam Tripura, Richard M Hoglund, Aung Pyae Phyo, Dysoley Lek, Akhter ul Islam, Anupkumar R Anvikar, Parthasarathi Satpathi, Sanghamitra Satpathi, Prativa Kumari Behera, Amar Tripura, Subrata Baidya, Marie Onyamboko, Nguyen Hoang Chau, Yok Sovann, Seila Suon, Sokunthea Sreng, Sivanna Mao, Savuth Oun, Sovannary Yen, Chanaki Amaratunga, Kitipumi Chutasmit, Chalermpon Saelow, Ratchadaporn Runcharern, Weerayuth Kaewmok, Nhu Thi Hoa, Ngo Viet Thanh, Borimas Hanboonkunupakarn, James J Callery, Akshaya Kumar Mohanty, James Heaton, Myo Thant, Kripasindhu Gantait, Tarapada Ghosh, Roberto Amato, Richard D Pearson, Christopher G Jacob, Sónia Gonçalves, Mavuto Mukaka, Naomi Waithira, Charles J Woodrow, Martin P Grobusch, Michele van Vugt, Rick M Fairhurst, Phaik Yeong Cheah, Thomas J Peto, Lorenz von Seidlein, Mehul Dhorda, Richard J Maude, Markus Winterberg, Nguyen Thanh Thuy-Nhien, Dominic P Kwiatkowski, Mallika Imwong, Podjanee Jittamala, Khin Lin, Tin Maung Hlaing, Kesinee Chotivanich, Rekol Huy, Caterina Fanello, Elizabeth Ashley, Mayfong Mayxay, Paul N Newton, Tran Tinh Hien, Neena Valecha, Frank Smithuis, Sasithon Pukrittayakamee, Abul Faiz, Olivo Miotto, Joel Tarning, Nicholas P J Day, Nicholas J White, Arjen M Dondorp, Rob W van der Pluijm, Rupam Tripura, Richard M Hoglund, Aung Pyae Phyo, Dysoley Lek, Akhter ul Islam, Anupkumar R Anvikar, Parthasarathi Satpathi, Sanghamitra Satpathi, Prativa Kumari Behera, Amar Tripura, Subrata Baidya, Marie Onyamboko, Nguyen Hoang Chau, Yok Sovann, Seila Suon, Sokunthea Sreng, Sivanna Mao, Savuth Oun, Sovannary Yen, Chanaki Amaratunga, Kitipumi Chutasmit, Chalermpon Saelow, Ratchadaporn Runcharern, Weerayuth Kaewmok, Nhu Thi Hoa, Ngo Viet Thanh, Borimas Hanboonkunupakarn, James J Callery, Akshaya Kumar Mohanty, James Heaton, Myo Thant, Kripasindhu Gantait, Tarapada Ghosh, Roberto Amato, Richard D Pearson, Christopher G Jacob, Sónia Gonçalves, Mavuto Mukaka, Naomi Waithira, Charles J Woodrow, Martin P Grobusch, Michele van Vugt, Rick M Fairhurst, Phaik Yeong Cheah, Thomas J Peto, Lorenz von Seidlein, Mehul Dhorda, Richard J Maude, Markus Winterberg, Nguyen T Thuy-Nhien, Dominic P Kwiatkowski, Mallika Imwong, Podjanee Jittamala, Khin Lin, Tin Maung Hlaing, Kesinee Chotivanich, Rekol Huy, Caterina Fanello, Elizabeth Ashley, Mayfong Mayxay, Paul N Newton, Tran Tinh Hien, Neena Valeche, Frank Smithuis, Sasithon Pukrittayakamee, Abul Faiz, Olivo Miotto, Joel Tarning, Nicholas PJ Day, Nicholas J White, Arjen M Dondorp
Journal: The Lancet (2020)

Artemisinin and partner-drug resistance in Plasmodium falciparum are major threats to malaria control and elimination. Triple artemisinin-based combination therapies (TACTs), which combine existing co-formulated ACTs with a second partner drug that is slowly eliminated, might provide effective treatment and delay emergence of antimalarial drug resistance.
A phase I study of oxaliplatin, full-dose gemcitabine and concurrent radiation therapy in patients with pancreatic cancer
Authors: S. P. Desai, E. Ben-Josef, T. J. Lawrence, I. R. Francis, J. K. Greenson, C. E. Alfred, L. M. Colletti, D. M. Simeone, D. P. Normolle, M. M. Zalupski
Journal: Journal of Clinical Oncology (2006)

4107 Background: We previously demonstrated safety and efficacy of full dose gemcitabine (GEM) and radiation therapy (RT) in patients (pts) with pancreatic cancer (PC). Our preclinical studies have shown that GEM with oxaliplatin (OX) preserves radiosensitization with synergistic cytotoxicity. To enhance local and systemic treatment effects, we initiated a study of OX and GEM with concurrent RT. Methods: Pts with untreated PC received up to 4 cycles of GEM day 1, 8, 15 and OX days 1, 15 repeated at 28 day intervals. RT (27 Gy in 1.8 Gy fractions to gross tumor volume with 1 cm margin) was given during cycle 1 and repeated in cycle 4. Surgery occurred after cycle 2 in resectable pts. Dose escalation was guided using time-to-event continuous reassessment method (TITE-CRM). Dose levels 1–4 GEM 1 g/m 2 IV over 30 min and OX 40, 55, 70, 85 mg/m 2 IV over 90 min; dose level 5, 6 OX dose remained 85 mg/m 2 but infusion time for GEM 1 g/m 2 was increased to 65, 100 min, respectively. Trial objective is to determine dose level associated with DLT thru cycle 2 in ≤ 20% of pts; planned accrual is 40 pts evaluable for DLT. Results: 40 pts have been enrolled (median age 63, men/women 26/14) with resectable (10), unresectable (27), and metastatic (3) PC. 29 pts have completed 2 cycles and 11 pts 4 cycles. After 2 cycles CA19–9 decreased &gt; 50% in 14 of 24 evaluable pts (58%). Six of 8 explored pts underwent margin negative resection with 1 path CR and 2 with small residual microscopic foci only. Per RECIST, CT response of the primary lesion after 2 cycles included 3 PR, 23 SD and 1 PD. Two additional PR were seen after cycle 4. Thirty pts are presently evaluable for DLT; 7 pts have suffered DLT including grade 4 platelets (4), decline in PS (2), GI bleed (1) and grade 3 weight loss (1). Current estimated probability of DLT is 21% (95% CI 11%,34%) for dose level 3 and 24% (95% CI 13%,37%) for dose level 4. Conclusions: The addition of OX 70–85 mg/m 2 days 1, 15 to full dose GEM based RT is tolerable and efficacious. A neoadjuvant phase II study in resectable PC using the MTD defined in this phase I study is planned. Supported by Sanofi-Aventis. [Table: see text]