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Nathan Goodyear

Evolving landscape of human epidermal growth factor receptor 2-positive breast cancer t... - 0 views

www.sciencedirect.com/...S0960977617300103

HER-2 breast cancer cancer herceptin Perjeta

shared by Nathan Goodyear on 06 Aug 18 - No Cached
  • 15%–20%
  • key mediator of cell growth, differentiation, and survival
  • of higher histological grade and are more likely to invade axillary lymph nodes
  • ...15 more annotations...
  • shortened survival and an increased risk of disease recurrence and metastasis
  • Currently, four HER2-directed agents are approved for the treatment of patients with HER2+ breast cancer: trastuzumab, pertuzumab, lapatinib, and ado-trastuzumab emtansine (T-DM1)
  • biosimilars
  • trastuzumab may provide greater benefit when administered concurrently with chemotherapy rather than after, and this has become the standard approach
  • concurrent use of anthracyclines (ie, doxorubicin or epirubicin) and trastuzumab is not recommended because of an increased risk for cardiac toxicity
    • Nathan Goodyear
      Nathan Goodyear on 06 Aug 18
       
      avoid herceptin in conjuction with antracyclines i.e. doxorubicin
  • Sequential doxorubicin plus cyclophosphamide followed by concomitant paclitaxel or docetaxel and trastuzumab is recommended for most patients
    • Nathan Goodyear
      Nathan Goodyear on 06 Aug 18
       
      top recommended regimen combination
  • Guidelines also recommend trastuzumab in combination with paclitaxel, docetaxel and carboplatin, or docetaxel and cyclophosphamide, particularly for patients with increased risk for cardiac toxicity or those with small (≤1 cm), node-negative HER2+ tumors
    • Nathan Goodyear
      Nathan Goodyear on 06 Aug 18
       
      good alternative in patients with increased risk of cardiac toxicity.
  • guidelines recommend up to 1 year of adjuvant trastuzumab
  • Neoadjuvant chemotherapy with trastuzumab is associated with higher rates of pathologic complete response (pCR) than chemotherapy alone or in combination with lapatinib
  • the combination of trastuzumab, lapatinib, and chemotherapy is not recommended because it failed to demonstrate noninferiority versus trastuzumab and chemotherapy in the adjuvant setting
  • recommend the combination of trastuzumab, pertuzumab, and chemotherapy as neoadjuvant treatment for patients with locally advanced HER2+ breast cancer and for some patients (node-positive or tumor ≥2 cm) with early-stage disease
  • neoadjuvant chemotherapy in combination with pertuzumab and trastuzumab reduced the risk of progression or death by 31% and recurrence or death by 40% versus trastuzumab alone
  • Concurrent chemotherapy and HER2-directed therapy improves survival outcomes over chemotherapy alon
  • dual inhibition of HER2 with trastuzumab and pertuzumab in combination with paclitaxel reduced the risk of death or progression by approximately 40% compared with concurrent trastuzumab and paclitaxel
  • the combination of trastuzumab, pertuzumab, and taxane chemotherapy is the preferred first-line regimen
  • Nathan Goodyear on 06 Aug 18
     
    HER-2 + breast cancer = appx 15-20% of all breast cancers and is a marker of worse prognosis and an indication for targeted immunotherapy blockade.
Nathan Goodyear

The Intestinal Microbiota Modulates the Anticancer Immune Effects of Cyclophosphamide - 0 views

www.sciencemag.org/...971

chemotherapy gut microbiota bacteria cancer

shared by Nathan Goodyear on 04 Dec 13 - No Cached
  • Nathan Goodyear on 04 Dec 13
     
    Animal study finds that the chemo drug cyclophosphamide needs the gut microbiota to deliver the anticancer immune response.  Disruption of the gut microbiota will reduce this anti-cancer effect and render chemo less effective or worse even ineffective
Nathan Goodyear

Targeted therapy with propranolol and metronomic chemotherapy combination: sustained co... - 0 views

www.ncbi.nlm.nih.gov/...PMC4303616

angiosarcoma breast cancer

shared by Nathan Goodyear on 12 Jan 21 - No Cached
  • Nathan Goodyear on 12 Jan 21
     
    Interesting case study using celecoxib, metronomic chemo (etoposide and cyclophosphamide) and Propranolol with positive results.
Nathan Goodyear

Insulin-induced enhancement of MCF-7 breast cancer cell response to 5-fluorou... - 0 views

journals.sagepub.com/...1010428317702901

IPT insulin potentiated therapy cancer

shared by Nathan Goodyear on 02 Oct 18 - No Cached
  • Nathan Goodyear on 02 Oct 18
     
    Study finds that insulin potentiates chemo cytotoxic therapy in MCF-7 breast cancer cell lines.
Nathan Goodyear

Adenoid cystic carcinoma: current therapy and potential therapeutic advances based on g... - 0 views

www.ncbi.nlm.nih.gov/...PMC4741919

adenoid cystic carcinoma

shared by Nathan Goodyear on 03 Oct 18 - No Cached
  • Cisplatin and 5-FU or CAP (cisplatin, doxorubicin, and cyclophosphamide) regimens can be used for combination chemotherapy
  • patients with advanced salivary gland malignancy treated with the CAP regimen achieved partial response (PR) or stable disease (SD) rates of 67% (8 out of 12 patients)
  • Agents commonly given as monotherapy for treating ACC are cisplatin, mitoxantrone, epirubicin, vinorelbine, paclitaxel, and gemcitabine. However, few of these agents have shown efficacy
  • ...23 more annotations...
  • single agent mitoxantrone or vinorelbine were recommended as reasonable choices
  • ACC is subdivided into 3 histological groups based on solid components of the tumor including cribriform, tubular, and solid
  • Cribriform and tubular ACCs usually exhibit a more indolent course, whereas the solid subtype is associated with worse prognosis
  • ACC consists of two different cell types: inner luminal epithelial cells and outer myoepithelial cells
  • epithelial cells express c-kit, cox-2 and Bcl-2
  • myoepithelial cells express EGFR and MYB
  • a balanced translocation of the v-myb avian myeloblastosis viral oncogene homolog-nuclear factor I/B (MYB-NFIB) is considered to be a signature molecular event of ACC oncogenesis
  • As a transcription factor, MYB is known to modulate multiple genetic downstream targets involved in oncogenesis, such as cox-2, c-kit, Bcl-2 and BclX
  • Various signaling cascades are essential for cancer cells to survive and grow. The PI3K/Akt/mTOR pathway is one of them
  • This pathway regulates cell survival and growth and is upregulated in many cancers
  • Mutations in genes associated with DNA repair are frequently found in familial cancer syndromes, such as hereditary breast-ovarian cancer syndrome (HBOC), hereditary non-polyposis colorectal cancer (HNPCC, also called Lynch syndrome) and Li-Fraumeni syndrome [30, 31]. These mutations were also reported in non-hereditary cancers
  • 70% of ACC samples (58 of 84) were found to have genetic alterations in the MYB/MYC pathway, indicating that changes in this pathway are crucial in ACC pathogenesis
  • The second most frequently mutated pathway was involved in chromatin remodeling (epigenetic modification), a pathway that includes multiple histone related proteins, and was altered in 44% of samples
  • C-kit
  • VEGF, iNOS and NF-κB were noted to be highly expressed in ACC cells as compared to normal salivary gland cells
  • members of the SOX family, such as SOX 4 and SOX10, are overexpressed in ACC
  • FABP7 (Fatty acid binding protein 7) and AQP1 (Aquaporin 1) tend to be overexpressed in ACC cell lines
  • considerable variability in HER2 overexpression ranging from 0–58% in patients with ACC
  • the study with cetuximab and concurrent chemoradiation or chemotherapy showed the highest ORR (total 43%, 9.5% CR and 33% PR), but this regimen was only given to the EGFR positive patients
  • Cancer immunotherapy can be classified into 3 major groups. Active immunization using anti-tumor vaccines to induce and recruit T cells, passive immunization based on monoclonal antibodies, and adoptive cell transfer to expand tumor-reactive autologous T cells ex vivo and then reintroduce these cells into the same individual
  • LAK cells showed cytotoxicity against ACC cells
  • cytokine-induced cell apoptosis and the cytotoxic effect of the LAK cells contributed to tumor regression
  • molecular finding of the MYB-NFIB fusion gene has the greatest potential to target what appears to be a fundamental event in disease pathogenesis
  • Nathan Goodyear on 03 Oct 18
     
    good review of adenoid cystic carcinoma
Nathan Goodyear

Clinical review: Specific aspects of acute renal failure in cancer patients - 0 views

www.ncbi.nlm.nih.gov/...PMC1550893

cancer renal failure

shared by Nathan Goodyear on 13 Aug 18 - No Cached
  • uric acid crystal formation in the renal tubules secondary to hyperuricaemia
  • calcium phosphate deposition related to hyperphosphataemia
  • usually develops shortly after the initiation of cytotoxic chemotherapy
  • ...18 more annotations...
  • Non-recombinant urate oxidase (Uricozyme®)
  • recombinant urate oxidase (Rasburicase®)
  • urine alkalisation may induce calcium phosphate deposition
  • renal replacement therapy should be started on an emergency basis when hydration fails to produce a prompt metabolic improvement or when ARF develops
  • Up to 50% of patients with newly diagnosed multiple myeloma have renal failure and up to 10% require dialysis
  • renal ultrasonography remains the method of choice for investigating extra-renal obstruction
  • The relief of the obstruction, either by percutaneous nephrostomy or through a ureteral stent, is the cornerstone of treatment
  • TMA may be associated with the cancer itself, with cancer chemotherapy, or with allogeneic BMT
  • thrombotic microangiopathy (TMA)
  • it may be as high as 5%
  • Most of the cases occur in patients with solid tumours, the most common type being adenocarcinoma (stomach, breast and lung)
  • The pathophysiology of the TMA-malignancy association remains controversial, although many studies suggest an insult to the vascular endothelium
  • mitomycin C. Subsequently, TMA has been reported with many anti-cancer agents, including gemcita-bine, bleomycin, cisplatin, CCNU, cytosine arabinoside, daunorubicin, deoxycoformycin, 5-FU, azathioprine and interferon α
  • Plasma exchanges have been shown to improve prognosis in the general population of patients with TMA
  • Causative factors should be looked for and antihypertensive treatment given. Lastly, in the absence of guidelines, we believe that plasma exchange should be proposed in patients with severe cancer treatment-associated TMA
  • The most widely used protective measure is saline infusion to induce solute diuresis
  • During methotrexate infusion and elimination, fluids should be given to maintain a high urinary output and urinary alkalisation should be performed to keep the urinary pH above 7.5. Rescue with folinic acid (50 mg four times a day) should be started 24 hours after each high-dose metho-trexate infusion and serum methotrexate concentrations should be measured every day
  • cyclophosphamide and ifosfamide
  • Nathan Goodyear on 13 Aug 18
     
    cancer and renal failure
Nathan Goodyear

Antitumor immunity of low-dose cyclophosphamide: changes in T cells and cytokines TGF-b... - 0 views

www.ncbi.nlm.nih.gov/...PMC7034239

IL-10 TGF-beta Treg low-dose chemotherapy cancer

shared by Nathan Goodyear on 19 Aug 20 - No Cached
  • Nathan Goodyear on 19 Aug 20
     
    Low dose cytoxan effects both local and systemic immune system.
Nathan Goodyear

A Comparative Analysis of Low-Dose Metronomic Cyclophosphamide Reveals Absent or Low-Gr... - 0 views

cancerres.aacrjournals.org/...3994

maximum tolerated chemotherapy cancer low-dose chemotherapy

shared by Nathan Goodyear on 31 Aug 20 - No Cached
  • Nathan Goodyear on 31 Aug 20
     
    Low-dose chemotherapy significantly reduced toxicity compared to maximum tolerated dosing.
Nathan Goodyear

VEGF receptor inhibitors block the ability of metronomically dosed cyclophosphamide to ... - 0 views

www.ncbi.nlm.nih.gov/...PMC3294103

low-dose chemotherapy glioblastoma multiforme VEGF glioblastoma cancer metronomic chemotherapy

shared by Nathan Goodyear on 11 Nov 20 - No Cached
  • Nathan Goodyear on 11 Nov 20
     
    CPA administered on an intermittent, every 6-day metronomic schedule stimulates tumor recruitment of macrophages, natural killer (NK) cells, and dendritic cells with regression of large established tumors, as seen in several implanted glioma models; also of note, VEGF inhibition inhibited this effect.
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