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https://www.readbyqxmd.com/read/28323034/co-targeting-of-egfr-and-autophagy-signaling-is-an-emerging-treatment-strategy-in-metastatic-colorectal-cancer
#1
Evangelos Koustas, Michalis V Karamouzis, Chrysovalantou Mihailidou, Dimitrios Schizas, Athanasios G Papavassiliou
The epidermal growth factor receptor (EGFR) and its associated pathway is a critical key regulator of CRC development and progression. The monoclonal antibodies (MoAbs) cetuximab and panitumumab, directed against EGFR, represent a major step forward in the treatment of metastatic Colorectal cancer (mCRC), in terms of progression-free survival and overall survival in several clinical trials. However, the activity of anti-EGFR moAbs appears to be limited to a subset of patients with mCRC. Studies have highlighted that acquired-resistance to anti-EGFR MoAbs biochemically converge into Ras/Raf/Mek/Erk and PI3K/Akt/mTOR pathways...
March 18, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28284575/mfolfox6-plus-panitumumab-versus-5-fu-lv-plus-panitumumab-after-six-cycles-of-frontline-mfolfox6-plus-panitumumab-a-randomized-phase-ii-study-of-patients-with-unresectable-or-advanced-recurrent-ras-wild-type-colorectal-carcinoma-sapphire-study-design-and%C3%A2-rationale
#2
Naoki Nagata, Hideyuki Mishima, Shuichi Kurosawa, Koji Oba, Junichi Sakamoto
BACKGROUND: In Japan, oxaliplatin (OXA)/5-fluorouracil (5-FU)/leucovorin (LV)-the mFOLFOX6 regimen-is the most frequently used first-line chemotherapy backbone for metastatic colorectal cancer. However, peripheral nerve disorders caused by OXA during mFOLFOX6 therapy can decrease patients' quality of life. OXA can be safely discontinued from a FOLFOX regimen after 6 cycles during first-line therapy. Also, for patients who discontinue OXA without having experienced peripheral nerve disorders, reintroducing OXA in the later stages of treatment could remain an option...
March 1, 2017: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/28282789/a-randomized-phase-iii-study-of-combining-erlotinib-with-bevacizumab-and-panitumumab-versus-erlotinib-alone-as-second-line-therapy-for-chinese-patients-with-non-small-cell-lung-cancer
#3
Ying Wang, Hui Wang, Yiling Jiang, Yaping Zhang, Xiaoyan Wang
PURPOSE: In this phase III clinical study, we assessed the clinical outcomes of combining erlotinib with bevacizumab and panitumumab as second-line chemotherapy for patients with non-small-cell lung cancer (NSCLC). METHODS: Chinese NSCLC patients, who received first-line platinum-based chemotherapy but still experienced disease progression, were assigned to receive second-line treatment of erlotinib plus bevacizumab and panitumumab (arm I), or erlotinib plus placebo (arm II)...
March 6, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28280605/next-generation-sequencing-identifies-interactome-signatures-in-relapsed-and-refractory-metastatic-colorectal-cancer
#4
Benny Johnson, Laurence Cooke, Daruka Mahadevan
BACKGROUND: In the management of metastatic colorectal cancer (mCRC), KRAS, NRAS and BRAF mutational status individualizes therapeutic options and identify a cohort of patients (pts) with an aggressive clinical course. We hypothesized that relapsed and refractory mCRC pts develop unique mutational signatures that may guide therapy, predict for a response and highlight key signaling pathways important for clinical decision making. METHODS: Relapsed and refractory mCRC pts (N=32) were molecularly profiled utilizing commercially available next generation sequencing (NGS) platforms...
February 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28245681/-does-the-sidedness-determine-the-first-line-treatment-of-irresectable-metastatic-colorectal-cancer
#5
Tamás Kullmann, István Sipőcz, Tamás Pintér
INTRODUCTION AND AIM: Median life expectancy of non-resectable metastatic colorectal cancer may surpass three years. However, several points of the treatment strategy are subject of ongoing debate. Optimal sequence of targeted agents is not elucidated either. Based on retrospective analyses of six clinical studies and a metaanalysis, the superiority of anti-EGFR agents such as cetuximab and panitumumab over anti-VEGF bevacizumab has been proposed in the treatment of left sided tumours...
March 2017: Orvosi Hetilap
https://www.readbyqxmd.com/read/28242452/top-down-analysis-of-immunoglobulin-g-isotypes-1-and-2-with-electron-transfer-dissociation-on-a-high-field-orbitrap-mass-spectrometer
#6
Luca Fornelli, Daniel Ayoub, Konstantin Aizikov, Xiaowen Liu, Eugen Damoc, Pavel A Pevzner, Alexander Makarov, Alain Beck, Yury O Tsybin
The increasing importance of immunoglobulins G (IgGs) as biotherapeutics calls for improved structural characterization methods designed for these large (~150kDa) macromolecules. Analysis workflows have to be rapid, robust, and require minimal sample preparation. In a previous work we showed the potential of Orbitrap Fourier transform mass spectrometry (FTMS) combined with electron transfer dissociation (ETD) for the top-down investigation of an intact IgG1, resulting in ~30% sequence coverage. Here, we describe a top-down analysis of two IgGs1 (adalimumab and trastuzumab) and one IgG2 (panitumumab) performed with ETD on a mass spectrometer equipped with a high-field Orbitrap mass analyzer...
February 24, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28237539/rationale-for-and-design-of-the-paradigm-study-randomized-phase-iii-study-of-mfolfox6-plus-bevacizumab-or-panitumumab-in-chemotherapy-na%C3%A3-ve-patients-with-ras-kras-nras-wild-type-metastatic-colorectal%C3%A2-cancer
#7
Takayuki Yoshino, Hiroyuki Uetake, Katsuya Tsuchihara, Kohei Shitara, Kentaro Yamazaki, Eiji Oki, Takeo Sato, Takeshi Naitoh, Yoshito Komatsu, Takeshi Kato, Kazunori Yamanaka, Kouji Iwasaki, Jumpei Soeda, Masamitsu Hihara, Takeharu Yamanaka, Atsushi Ochiai, Kei Muro
BACKGROUND: It remains unclear whether an anti-VEGF or anti-EGFR antibody with standard doublet chemotherapy is the optimal first-line treatment in patients with RAS (KRAS/NRAS) wild-type metastatic colorectal cancer (mCRC). Here we outline the PARADIGM study (NCT02394795), designed to evaluate the superiority of panitumumab over bevacizumab, in combination with oxaliplatin/5-fluorouracil/leucovorin (mFOLFOX6) in patients with RAS wild-type chemotherapy-naïve mCRC. PATIENTS AND METHODS: Eligible patients are aged 20 to 79 years with an ECOG performance status of 0-1 and histologically/cytologically confirmed RAS wild-type mCRC...
January 24, 2017: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/28229371/overall-survival-and-metastasis-resections-in-patients-with-metastatic-colorectal-cancer-using-electronic-medical-records
#8
Eetu Heervä, Maija Lavonius, Panu Jaakkola, Heikki Minn, Raija Ristamäki
PURPOSE: Treatment for patients with metastatic colorectal cancer is chemotherapy commonly combined with monoclonal antibodies against vascular endothelial growth factor (bevacizumab) or epidermal growth factor receptor (cetuximab or panitumumab), the efficacy of which has been proven in randomized controlled trials. The objective of the current retrospective study was to analyze the impact of targeted therapy, adverse events, and dose reduction on overall survival (OS) and metastasis resection rates...
February 23, 2017: Journal of Gastrointestinal Cancer
https://www.readbyqxmd.com/read/28228152/cardiac-metastasis-from-colon-cancer-effectively-treated-with-5-fluorouracil-leucovorin-and-oxaliplatin-modified-folfox6-plus-panitumumab-a-case-report
#9
Yoshiki Tsujii, Yoshito Hayashi, Akira Maekawa, Tetsuji Fujinaga, Kengo Nagai, Shunsuke Yoshii, Akihiko Sakatani, Satoshi Hiyama, Shinichiro Shinzaki, Hideki Iijima, Tetsuo Takehara
BACKGROUND: Cardiac metastasis from colorectal cancer is rare. There is little evidence supporting the effectiveness of chemotherapy, and standard therapy for metastatic cardiac tumors has not been established. CASE PRESENTATION: A 76-year-old woman presented with a right ventricle tumor that was detected incidentally on screening cardiac ultrasonography. The initial computed tomography (CT) scan showed the cardiac tumor, which was approximately 40 mm in size, and multiple pulmonary nodules...
February 23, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28220486/cetuximab-plus-irinotecan-versus-panitumumab-in-patients-with-refractory-metastatic-colorectal-cancer-in-ontario-canada
#10
Katarzyna J Jerzak, Scott Berry, Yoo-Joung Ko, Craig Earle, Kelvin K W Chan
The addition of irinotecan to an epidermal growth factor receptor (EGFR) antibody has previously been shown to improve tumor response rate and time to progression but not overall survival (OS) for refractory metastatic colorectal cancer (mCRC). We assessed the "real-world" effectiveness and toxicity of the combination versus monotherapy. In Ontario, Canada, universal public funding is available for either cetuximab plus irinotecan (Cmab + I) combination therapy or panitumumab (Pmab) monotherapy, only in patients with refractory nonmutated RAS mCRC...
May 1, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28199979/atm-mutations-and-e-cadherin-expression-define-sensitivity-to-egfr-targeted-therapy-in-colorectal-cancer
#11
Anna-Lena Geißler, Miriam Geißler, Daniel Kottmann, Lisa Lutz, Christiane D Fichter, Ralph Fritsch, Britta Weddeling, Frank Makowiec, Martin Werner, Silke Lassmann
EGFR-targeted therapy is a key treatment approach in patients with RAS wildtype metastatic colorectal cancers (CRC). Still, also RAS wildtype CRC may be resistant to EGFR-targeted therapy, with few predictive markers available for improved stratification of patients. Here, we investigated response of 7 CRC cell lines (Caco-2, DLD1, HCT116, HT29, LS174T, RKO, SW480) to Cetuximab and correlated this to NGS-based mutation profiles, EGFR promoter methylation and EGFR expression status as well as to E-cadherin expression...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28198009/endoscopic-ultrasound-guided-fine-needle-aspirate-derived-preclinical-pancreatic-cancer-models-reveal-panitumumab-sensitivity-in-kras-wild-type-tumors
#12
William Berry, Elizabeth Algar, Beena Kumar, Christopher Desmond, Michael Swan, Brendan J Jenkins, Daniel Croagh
Pancreatic cancer (PC) is largely refractory to existing therapies used in unselected patient trials, thus emphasizing the pressing need for new approaches for patient selection in personalized medicine. KRAS mutations occur in 90% of PC patients and confer resistance to epidermal growth factor receptor (EGFR) inhibitors (e.g., panitumumab), suggesting that KRAS wild-type PC patients may benefit from targeted panitumumab therapy. Here, we use tumor tissue procured by endoscopic ultrasound-guided fine-needle aspirate (EUS-FNA) to compare the in vivo sensitivity in patient-derived xenografts (PDXs) of KRAS wild-type and mutant PC tumors to panitumumab, and to profile the molecular signature of these tumors in patients with metastatic or localized disease...
February 15, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28186982/avidinox-anchored-biotinylated-trastuzumab-and-pertuzumab-induce-down-modulation-of-erbb2-and-tumor-cell-death-at-concentrations-order-of-magnitude-lower-than-not-anchored-antibodies
#13
Ferdinando Maria Milazzo, Anna Maria Anastasi, Caterina Chiapparino, Antonio Rosi, Barbara Leoni, Loredana Vesci, Fiorella Petronzelli, Rita De Santis
The oxidized version of Avidin, known as AvidinOX, was previously shown to link to tissue proteins upon injection or nebulization, thus becoming a stable receptor for biotinylated therapeutics. AvidinOX is currently under clinical investigation to target radioactive biotin to inoperable tumor lesions (ClinicalTrials.gov NCT02053324). Presently, we show that the anti-ErbB2 monoclonal antibodies Trastuzumab and Pertuzumab can be chemically biotinylated while maintaining their biochemical and biological properties...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28152526/egfr-inhibitors-in-patients-with-advanced-squamous-cell-anal-carcinomas-a-single-institution-experience
#14
Dae Won Kim, Jennifer Byer, Nishi Kothari, Amit Mahipal, Yound Doo Chang, Richard D Kim
BACKGROUND: Although squamous cell anal carcinomas are relatively rare, their incidence has been increasing steadily. Because of the limited data, treatment of metastatic disease is a major therapeutic challenge. In this study, we report the safety and efficacy of epidermal growth factor receptor (EGFR) inhibitors in patients with advanced squamous cell anal carcinomas. METHOD: A retrospective analysis was conducted using the Moffitt Cancer Tumor Registry from January 2009 to January 2014...
February 3, 2017: Oncology
https://www.readbyqxmd.com/read/28151706/near-infrared-photoimmunotherapy-in-a-transgenic-mouse-model-of-spontaneous-epidermal-growth-factor-receptor-egfr-expressing-lung-cancer
#15
Yuko Nakamura, Zoe Weaver Ohler, Deborah Householder, Tadanobu Nagaya, Kazuhide Sato, Shuhei Okuyama, Fusa Ogata, Dagane Daar, Tieu Hoa, Peter L Choyke, Hisataka Kobayashi
Near infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that combines the specificity of antibodies for targeting tumors with the toxicity induced by a sensitive photoabsorber following exposure to NIR light. Most studies of NIR-PIT have been performed in xenograft models of cancer. The purpose of this study was to evaluate the therapeutic effects of NIR-PIT in a transgenic model of spontaneous lung cancer expressing human EGFR (hEGFR-TL). Mice were separated into 3 groups for the following treatments: (1) no treatment (control); (2) 150 μg of photoabsorber, IR700, conjugated to panitumumab, an antibody targeting EGFR [antibody-photoabsorber conjugate (APC)] intravenously (i...
February 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28138221/immunotherapy-for-the-treatment-of-colorectal-tumors-focus-on-approved-and-in-clinical-trial-monoclonal-antibodies
#16
REVIEW
Alex Françoso, Patricia Ucelli Simioni
Colorectal cancer is considered a disease of the elderly population. Since the number of geriatric patients continues to rise, monoclonal antibody therapy is the most promising therapy in the recent research. Presently, the monoclonal antibodies most frequently used in the treatment of colorectal tumors are bevacizumab, cetuximab, panitumumab, and ramucirumab. Bevacizumab is a monoclonal antibody that acts on VEGF. Cetuximab and panitumumab act on EGFR. Ramucirumab binds directly to the ligand-binding pocket of VEGFR-2 to block the binding of VEGF-A, VEGF-C, and VEGF-D...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28135678/curative-resection-for-locally-advanced-sigmoid-colon-cancer-using-neoadjuvant-chemotherapy-with-folfox-plus-panitumumab-a-case-report
#17
Kenji Tomizawa, Yuji Miura, Yudai Fukui, Yutaka Hanaoka, Shigeo Toda, Jin Moriyama, Naoko Inoshita, Yukinori Ozaki, Toshimi Takano, Shuichiro Matoba, Hiroya Kuroyanagi
INTRODUCTION: FOLFOX and panitumumab combined chemotherapy plays an important role for metastatic colorectal cancer. However the usefulness of this regimen for neoadjuvant therapy is unclear. CASE REPORT: A 67-year-old man with abdominal pain and pneumaturia was diagnosed with RAS wild-type sigmoid colon cancer with urinary bladder invasion and colovesical fistulas. Because the cancer was considered to be unresectable, a transverse-loop colostomy was performed. Colonoscopy and computed tomography revealed a marked reduction in the size of the primary tumor after six courses of FOLFOX4 (oxaliplatin, leucovorin, and 5-fluorouracil) plus panitumumab...
January 17, 2017: International Journal of Surgery Case Reports
https://www.readbyqxmd.com/read/28133349/-long-term-survival-of-a-patient-with-sigmoid-colon-cancer-with-multiple-visceral-metastases
#18
Yoshiyuki Sasaki, Naoto Nishigori, Fumikazu Koyama, Takeshi Ueda, Takashi Inoue, Keijirou Kawasaki, Shinsaku Obara, Takayuki Nakamoto, Yasuyuki Nakamura, Hisao Fujii, Yoshiyuki Nakajima
A 66-year-old woman underwent total pelvic exenteration for a pelvic tumor. The pathological diagnosis was sigmoid colon cancer T4b(in the small intestine, uterus, and vagina), N0, M0, Stage II . The patient was treated with XELOX for 6 months as adjuvant chemotherapy and was then treated with IRIS for another 6 months. Brain metastasis developed in the left occipital lobe after 12 months, and she underwent craniotomy and enucleation of the tumor. Liver metastasis and peritoneal dissemination metastasis developed 16 months after her initial diagnosis...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28133304/-a-case-of-metastatic-colorectal-cancer-with-her2-overexpression-amplification
#19
Akio Matsumoto, Yoshifumi Shimada, Ryoma Yagi, Kohei Miura, Yosuke Tajima, Takuma Okamura, Masato Nakano, Hitoshi Kameyama, Hitoshi Nogami, Satoshi Maruyama, Yasumasa Takii, Hiroshi Ichikawa, Jun Sakata, Takashi Kobayashi, Toshifumi Wakai
We report a case of panitumumab-resistant rectal cancer with HER2 gene amplification detected by CancerPlex®. A 51- year-old man was diagnosed with an obstructive rectal cancer having lung and adrenal metastases. He underwent the Hartmann 's operation, and KRAS mutations were not detected. After the surgery, 3 courses of CapeOx plus bevacizumab were administered as first-line chemotherapy; however, the lung and adrenal metastases progressed. Subsequently, 24 courses of IRIS/panitumumab was administered as second-line chemotherapy, and the metastases slowly progressed...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28133295/-a-systematic-analysis-of-oncogene-and-tumor-suppressor-genes-for-panitumumab-resistant-rectal-cancer-with-wild-ras-gene-a-case-report
#20
Yosuke Tajima, Yoshifumi Shimada, Ryoma Yagi, Takuma Okamura, Masato Nakano, Hitoshi Kameyama, Hitoshi Nogami, Satoshi Maruyama, Yasumasa Takii, Kohei Miura, Hiroshi Ichikawa, Masayuki Nagahashi, Jun Sakata, Takashi Kobayashi, Toshifumi Wakai
A 58-year-old man was admitted with the complaint of bloody stools. Colonoscopy and computed tomography revealed a rectal cancer with a liver metastasis and multiple lung metastases. After administering a regimen comprising 3 courses of XELOX plus bevacizumab chemotherapy, the sizes of the primary and metastatic lesions decreased remarkably. Abdominoperineal resection was performed for local control of the cancer; the specimen from the initial tumor was found to be KRAS wild type. After 14 courses of XELOX chemotherapy, brain metastases were detected...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
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