Significance of calorie-restricted ketogenic diet for lung cancer with brain metastases and hepatoma with pulmonary metastases: report of two cases

Cancer cells have altered metabolism that is characterized by an enhanced uptake and utilization of glucose. These increased glucose dependence alterations, present potential vulnerabilities that could be targeted for cancer therapy. The calorie-restricted ketogenic diet (KD) may meet the requirement. In this study, we explore the feasibility of the ketogenic diet as adjuvant therapy for cancer treatment. We present two cases of patients diagnosed with aggressive forms of cancer, lung cancer with brain metastatic tomours and primary liver cancer with pulmonary metastases. The patients began KD intervention after exhausting the other treatment options. Both of them responded to KD and demonstrated a beneficial effect. The tomour size from serial imaging and serum tumour markers were significantly reduced after KD in both subjects without any adverse effects. Both patients had tumour remission even after stopping the ketogenic diet, indicating that KD is a safe, effective treatment to aggressive cancers with metastases when used with conventional therapies.

Significance of calorie-restricted ketogenic diet for lung cancer with brain metastases and hepatoma with pulmonary metastases: report of two cases

Cancer cells have altered metabolism that is characterized by an enhanced uptake and utilization of glucose. These increased glucose dependence alterations, present potential vulnerabilities that could be targeted for cancer therapy. The calorie-restricted ketogenic diet (KD) may meet the requirement. In this study, we explore the feasibility of the ketogenic diet as adjuvant therapy for cancer treatment. We present two cases of patients diagnosed with aggressive forms of cancer, lung cancer with brain metastatic tomours and primary liver cancer with pulmonary metastases. The patients began KD intervention after exhausting the other treatment options. Both of them responded to KD and demonstrated a beneficial effect. The tomour size from serial imaging and serum tumour markers were significantly reduced after KD in both subjects without any adverse effects. Both patients had tumour remission even after stopping the ketogenic diet, indicating that KD is a safe, effective treatment to aggressive cancers with metastases when used with conventional therapies.

ONO-4059—a Potent and Selective Reversible Bruton’s Tyrosine Kinase (Btk) Inhibitor: Single Agent, Twice Daily (BD) Dosing and Dosing with Food Results in Sustained, High Trough Levels of ONO-4059, Translating into 100% Tumour Remission in a TMD-8 Xenograft Model

Purpose: Bruton’s tyrosine kinase (Btk) is a key regulator of the BCR signaling pathway and abberant BCR signaling has been implicated in the survival of malignant B-cells. The activated B-cell-like (ABC) sub-type of Diffuse Large B-Cell Lymphoma (DLBCL) correlates with poor prognosis. There is still a high unmet, medical need for new therapies, preferably chemo-sparing, to help treat patients with ABC-DLBCL and CLL as well as other B-cell malignancies. ONO-4059 is a highly selective, orally bioavailable inhibitor of Btk kinase activity with a potency (IC50) of 2.2 nM. ONO-4059 reversibly blocks BCR signaling and B-cell proliferation and activation. Data from the ongoing Phase 1 study (ONO-4059POE001), where ONO-4059 is administered as monotherapy (QD) demonstrated a best overall response rate of 47% (7/15) in non-GCB DLBCL patients (Walter et al, ASCO 2014; Rule et al, EHA 2014). We hypothesized that the efficacy of ONO-4059 could be further enhanced by increasing the drug trough concentration. To address this, we examined different dosing regimens of ONO-4059 in an ABC-DLBCL xenograft model. Methods: TMD-8 tumour cells (ABC-DLBCL cell line) were implanted sub-cutaneously into female SCID mice. Randomization of mice occurred when mean tumour volume was 100-200 or 400-450 mm3. ONO-4059 was administered orally or mixed in food at doses up to 20 mg/kg/day and animals were dosed QD or BD. Tumour volumes were measured twice a week after initiation of treatment, and tumour volumes were determined using the formula volume (= width2 x length)/2. Animals were euthanized when the tumours reached a maximum volume of 3,000 mm3. Results: For the100-200 mm3 tumour groups, tumour growth inhibition at the final treatment day was 23% in QD, 72.9% in BD and 100% in dose mixed in food, groups respectively. For the 400-450 mm3 tumour groups, no growth inhibition was observed in the QD group and, growth inhibitions of 27.5% in BD and 100% in dose mixed in food were observed. Interestingly, the treatment with ONO-4059-containing diets resulted in tumour remission in 10/10 animals, in both 100-200 and 400-450 mm3 treatment groups, whereas no tumour free animals were observed in the other treatment groups. The PK concentration and phosphorylated Btk (pBtk) inhibition levels of those animals whose dose was mixed in with food were higher than that of other treatment groups. Conclusion: Our previous study demonstrated that 100% tumour remission can be achieved partially with an ONO-4059 and GA101 or rituximab combination (Yoshizawa et al, ASH 2013). However, to date, no orally bioavailable targeted-agent administered as monotherapy has demonstrated 100% tumour remission in an advanced ABC-DLBCL xenograft model. Although the clinical data for ONO-4059 given as monotherapy (QD) is very encouraging in both relapsed and refractory CLL/NHL patients, this data indicates that a more frequent dosing regimen such as BD may be a more effective treatment, especially for non-GCB DLBCL and warrants further investigation in the clinical setting, along with food effect studies. Disclosures Yoshizawa: Ono Pharmaceutical Co., Ltd.: Employment. Yasuhiro:Ono Pharmaceutical Co., Ltd.: Employment. Honda:Ono Pharmaceutical Co., Ltd.: Employment. Kawabata:Ono Pharmaceutical Co., Ltd.: Employment.

Role of traditional medicines in the management of cancer

Context: Increasing numbers of cancer patients are looking towards traditional medicines (TM) in an effort to sustain tumour remission or halt the metastasis. TM such as Chinese Traditional Medicines, Ayurveda and Unani Medicines are being used in many parts of world from centuries. However, scientific data is lacking for the clinical use of majority of these medicines in cancer management and systematic clinical evaluation is mandatory before recommending long term use. Objective: The role of traditional medicine for prevention and management of cancer are reviewed in this paper which will help to take a step further to bring these TM into mainstream therapy. Methods: Traditional knowledge about the claims of therapeutic potential is collected. Emphasis was given to the use of plant derived products. Further efforts were made to identify the driving factors for use of such TM for the cure of cancer. Results: There are several driving factors which attract patients towards TM out of which minimum side effects of TM remains on the priority. Apart from being used as standalone therapy, TM is progressively becoming more popular as adjuvant therapy to improve effectiveness of conventional treatment and to reduce the side effects of chemotherapy or radiation therapy. Conclusion: Patients are inclining towards TM due to diverse reasons. The search for anticancer drugs from herbs has been very productive and advances in pharmacological techniques have exerted enormous drive on the research and development of new biologically active compounds of plant origin, which may act alone or in synergistic manner.

Different Strategies for Cancer Treatment: Mathematical Modelling

We formulate and analyse a mathematical model describing immune response to avascular tumour under the influence of immunotherapy and chemotherapy and their combinations as well as vaccine treatments. The effect of vaccine therapy is considered as a parametric perturbation of the model. In the case of a weak immune response, neither immunotherapy nor chemotherapy is found to cause tumour regression to a small size, which would be below the clinically detectable threshold. Numerical simulations show that the efficiency of vaccine therapy depends on both the tumour size and the condition of immune system as well as on the response of the organism to vaccination. In particular, we found that vaccine therapy becomes more effective when used without time delay from a prescribed date of vaccination after surgery and is ineffective without preliminary treatment. For a strong immune response, our model predicts the tumour remission under vaccine therapy. Our study of successive chemo/immuno, immuno/chemo and concurrent chemoimmunotherapy shows that the chemo/immuno sequence is more effective while concurrent chemoimmunotherapy is more sparing.