Outcome of 67 patients with solid tumors relapsed after high-dose chemotherapy and peripheral blood stem cell transplantation

Bojko, Peter; Akça, Alper; Seeber, S.

doi:10.1038/sj.bmt.1704047

Cited by 2 publications

(1 citation statement)

References 18 publications

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“…Cancer cell survival and colony formation of irradiated cells after chemotherapeutic exposure or radiation therapy have been observed during cancer relapse . In addition to inhibition of cancer cell viability, CT‐1 is also capable of inhibiting the colony forming potential of breast cancer cells suggesting additional advantage of CT‐1.…”

Section: Discussionmentioning

confidence: 99%

New orally active DNA minor groove binding small molecule CT‐1 acts against breast cancer by targeting tumor DNA damage leading to p53‐dependent apoptosis

Saini

Ullah

Ashraf

et al. 2016

Molecular Carcinogenesis

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Targeting tumor DNA damage and p53 pathway is a clinically established strategy in the development of cancer chemotherapeutics. Majority of anti-cancer drugs are delivered through parenteral route for reasons like severe toxicity, lack of stability, and poor enteral absorption. Current DNA targeting drugs in clinical like anthracycline suffers from major drawbacks like cardiotoxicity. Here, we report identification of a new orally active small molecule curcumin-triazole conjugate (CT-1) with significant anti-breast cancer activity in vitro and in vivo. CT-1 selectively and significantly inhibits viability of breast cancer cell lines; retards cells cycle progression at S phase and induce mitochondrial-mediated cell apoptosis. CT-1 selectively binds to minor groove of DNA and induces DNA damage leading to increase in p53 along with decrease in its ubiquitination. Inhibition of p53 with pharmacological inhibitor as well as siRNA revealed the necessity of p53 in CT-1-mediated anti-cancer effects in breast cancer cells. Studies using several other intact p53 and deficient p53 cancer cell lines further confirmed necessity of p53 in CT-1-mediated anti-cancer response. Pharmacological inhibition of pan-caspase showed CT-1 induces caspase-dependent cell death in breast cancer cells. Most interestingly, oral administration of CT-1 induces significant inhibition of tumor growth in LA-7 syngeneic orthotropic rat mammary tumor model. CT-1 treated mammary tumor shows enhancement in DNA damage, p53 upregulation, and apoptosis. Collectively, CT-1 exhibits potent anti-cancer effect both in vitro and in vivo and could serve as a safe orally active lead for anti-cancer drug development. © 2016 Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 99%

New orally active DNA minor groove binding small molecule CT‐1 acts against breast cancer by targeting tumor DNA damage leading to p53‐dependent apoptosis

Saini

Ullah

Ashraf

et al. 2016

Molecular Carcinogenesis

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High-dose chemotherapy with autologous stem cell transplantation in patients with oligometastatic breast cancer

Bojko

Welt

Schleucher

et al. 2004

Bone Marrow Transplant

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Summary:The purpose of this prospective trial was to study a combined-modality treatment including local consolidation by surgery or radiotherapy and high-dose chemotherapy (HDC) followed by peripheral-blood stem-cell (PBSC) transplantation. In all, 48 patients with oligometastatic breast cancer amenable to local treatment after induction chemotherapy with epirubicin and cyclophosphamide or paclitaxel and cisplatin, depending on prior adjuvant chemotherapy, were enrolled. The median follow-up was 41 months (range, 7-85 months). PBSC were collected in 47 patients, and 40 received one or two courses of HDC. Local therapy was given in 37 patients. No treatment-related deaths occurred. Of 47 evaluable patients, 36 (75% of intention-to-treat population) had no evidence of disease or complete remission after completion of therapy. Six patients (12.5%) had partial response, two patients (4%) no change, and three patients (6%) progressive disease. The median time to progression and overall survival was 17.5 (95% confidence interval (CI), 14-21 months) and 42.2 months (95% CI, 33-52 months), respectively, and 27% of patients were progression free after 5 years. In conclusion, patients with oligometastatic breast cancer can be treated safely with this combined modality protocol with promising relapse-free survivals.

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Outcome of 67 patients with solid tumors relapsed after high-dose chemotherapy and peripheral blood stem cell transplantation

Cited by 2 publications

References 18 publications

New orally active DNA minor groove binding small molecule CT‐1 acts against breast cancer by targeting tumor DNA damage leading to p53‐dependent apoptosis

New orally active DNA minor groove binding small molecule CT‐1 acts against breast cancer by targeting tumor DNA damage leading to p53‐dependent apoptosis

High-dose chemotherapy with autologous stem cell transplantation in patients with oligometastatic breast cancer

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