Table 2.

Tumor Growth Studies

		METHODS					RESULTS
Study	Reference	Rodent Model	Tumor Type / Induction model	Exercise Protocol			Tumor Progression Results
Study	Reference	Rodent Model	Tumor Type / Induction model	Exercise Modality	Exercise Prescription Freq/week \| Dur \| Intens \| Length	Exercise Initiation	Tumor Progression Results
Daneryd, 1995	51	Female Wistar Furth rats	Leydig cell / 1.5mm³ injection of Leydig cell sarcoma (LTW)	Voluntary wheel running	13d	Immediately after injection	-EX ↓ tumor volume by 34%.
Daneryd, 1995	52	Female Wistar Furth rats	Leydig cell / 1.5mm³ injection of Leydig cell sarcoma (LTW) or Nitrosoguanine- induced adenocarcinoma s.c. into each flank	Voluntary wheel running	32d	Immediately after injection	- 13.4g vs 16.4g EX vs SED final LTW weights
Zhu, 2008	42	21d old female Sprague-Dawley rats	Mammary / 25 or 50 mg/kg MNU, i.p.	Voluntary wheel running	Voluntary wheel running for 8w	1w post-injection	-Tumor weight 0.62g vs. 1.16g (SED vs. EX)
Jones, 2010	57	3–4w old female athymic mice	Mammary / 1×10⁶ MDA-MB-231 cells, injected orthotopically	Voluntary wheel running	Voluntary wheel running for 41– 48d	2d post-implant	No change in primary tumor growth (EX ↑21%)
Yan, 2011	64	3w old male C57BL/6 mice	Lung / 2.5×10⁵/50 µl/mouse Lewis lung carcinoma cells s.c. lower dorsal region	Voluntary wheel running	Primary tumors excised at 1cm diameter, access to wheels continued for additional 2w.	9w before tumor implantation	-No difference in tumor cross-sectional area and tumor volume.
Jones, 2012	55	6–8w old male C57BL/6 mice	Prostate / 5×10⁵ mouse prostate C-1 cells, orthotopically	Voluntary wheel running	Wheel running for 8 weeks	14d after tumor transplant	-Primary tumor growth was comparable between groups
Goh, 2014	66	18m old Balb/cBy mice	Mammary / 1×10⁴ cells in 4^th mammary fat pad	Voluntary wheel running	Voluntary wheel running for 90 days	60 days prior to tumor transplant, followed by 30 days post-transplant	-Inverse relationship between distance run and final tumor mass
Betof, 2015	65	Female Balb/c or female C57Bl/6 mice	Mammary / 5×10⁵ 4T1-luc or 2.5×10⁵ E0771 cells in dorsal mammary fat pad	Voluntary wheel running	Voluntary wheel running beginning either 9 weeks prior to tumor transplant, or at the time of tumor transplant	SS: SED before and after transplant RS: EX for 9 weeks prior to transplant; SED after transplant SR: SED before transplant; EX after transplant RR: EX 9 weeks prior to transplant, continuing after transplant	- Growth rates of SS and RS were similar, and growth rates of SR and RR were similar - EX slowed tumor growth compared to SED (both tumor models)
Alessio, 2009	24	3w old female Sprague-Dawley rats	Spontaneous tumors	Voluntary wheel running or activity box	Wheel: every other day, 24h access throughout animals’ life. Activity box (PA): 1h in large activity box twice a week for life.	Spontaneous tumors, animals followed for life.	- EX ↓tumor growth rate
Colbert, 2009	26	Female heterozygous (p53+/−): MMTV-Wnt-1 transgenic mice	Mammary / Transgenic	Voluntary wheel running and forced treadmill running	Treadmill running: TREX 1: 5×\|45min\|20m/min at 5% grade\|until completion TREX 2: 5×\|45min\|24m/min at 5% grade\|until completion Voluntary wheel running with 24 hour access.	11w of age	- Time to tumor size of 1.5cm: 24.8d, 13.8d, and 19.5d in control, TREX1 and TREX2 animals. - Treadmill running led to faster tumor growth, no difference due to voluntary wheel running - Treadmill running ↓ survival
Newton, 1965	60	45d old Sprague- Dawley rats	Carcinoma / Equal volumes of Walker- 256 cells s.c. into the right flank.	Forced treadmill running	Pre-Tumor: 50h over 5d at 950ft/hr. Post-Tumor: 138h over 10d at 950 ft/hr.	5d before tumor implantation +/− 4d after tumor implantation	-EX ↓ final tumor weight vs SED control. -Early life manipulation + EX ↓ final tumor weight vs EX alone and SED.
Uhlenbruck, 1991	63	BALB/c mice	Sarcoma / 2.4×10⁴ L- 1 cells s.c.	Forced treadmill running	7×\|distances of 200m/400m/800m\|0.3m/s\|2w	4w before and 2w after injection	-200m group ↓ tumor weight
Woods, 1994	40	6w old male C3H/HeN mice	Mammary / 2.5 ×10⁵ mammary SCA-1 cells s.c. in the back.	Forced treadmill running	Treadmill running: Moderate: 7×\|30min\|18m/min at 5% grade\|1w. Exhaustive: 7×\|varied\|18m/min for 30min, then 3m/min↑ every 30min until exhausted\|1w	3d prior to injection.	No difference in growth rate of tumor size at time of euthanasia (two weels)
Whittal-Strange, 1998	39	21d old female Sprague-Dawley rats	Mammary / 37.5mg/kg NMU i.p. at 50d of age, (1 day after last bout of EX)	Forced treadmill running	Progressive training to 5×\|60min\|18 m/min at 15% grade\|4w	21d of age (29d prior to injection)	-Tumor growth rate at 22w post-NMU: 0.043g/day in SED vs. 0.107g/day in EX -Final tumor weight: (3.2g in SED vs. 1.2g in EX
Bacurau, 2000	49	12w old male Wistar rats	Carcinoma / 2×10⁷ Walker-256 cells s.c. in the flank	Forced treadmill running	5×\|60min\|60% of VO2 peak\|10w	8w prior to injection	-Day 15 tumor weight 1.82% vs 19% of BW (EX vs SED) -EX prolonged survival by 1.9 fold
Westerlind, 2003	37	21d old female Sprague-Dawley rats	Mammary / 25 or 50 mg/kg MNU, i.p.	Forced treadmill running	Week 1: 5×\|10–15min\|30m/min\|1w. Week 2–9: 5×\|30min\|23– 25m/min\|8w	1w post-injection	-↑ Latency in EX (35.8d vs. 33.1d). -No difference in median tumor-free survival time was observed in the EX versus sham-EX (SHAM), nor were there any differences in multiplicity at either a high or moderate dose of MNU
Zielinski, 2004	44	6–8w old female BALB/c mice	Neoplastic lymphoid cells / 2×10⁷ EL-4 cells s.c. in the back behind the neck	Forced treadmill running	7×\|3h or until volitional fatigue\|gradually increasing speed, 20–40m/min, 5% grade\|5–14d	First session immediately before injection.	-No difference in tumor density
Jones, 2005	56	3–4w old female athymic mice	Mammary / Flank injection of 5×10⁶ MDA-MB-231 cells	Forced treadmill running	5d/w\|10m/min for 10min up to 18m/min for 45 min\|0% grade\|8w	14d post-injection	-No change in tumor growth.
Bacurau, 2007	48	8w old male Wistar rats	Carcinoma / 2×10⁷ Walker-256 cells s.c. in the flank	Forced treadmill running	5×\|30min\|85% of VO₂ max\|10w	8w prior to injection	-Survival: 16d for SED, 45d for EX -EX tumors were 6.9% of final body mass vs. 17.33% for SED control.
Lira, 2008	58	Male Wistar rats	Carcinoma / 2×10⁷ Walker-256 cells s.c. in the flank	Forced treadmill running	5×\|60min\|60–65% of VO2 peak\|10w 2w pre-training period: rats ran progressively from 15 to 60min at 10m/min. Running was increased to 20m/min for two weeks after injection.	8w prior to injection	-Tumor weight: 17.2g in SED; 1.9g in EX
Murphy, 2011	59	4w old C3(1)SV40Tag mice	Mammary / Transgenic (tumors began developing at 12w of age).	Forced treadmill running	6×\|60m\|20m/min at 5%\|20w	4w of age	-Tumor volume: ↓ in EX at 21 and 22w.
Gueritat, 2014	69	10–12w old Copenhagen rats	Prostate / surgical s.c. implantation of R3327 Dunning AT1 tumor fragment	Forced treadmill running	5×\|15–60m\|20–25 m/min\|5w	15d after tumor implantation	- EX rats had smaller tumors at 14 and 21 days compared to SED controls - Tumor doubling time was significantly slower in EX vs. SED (6.19d vs. 8.81d)
Shalamzari, 2014	67	4–6w old Balb/c mice	Mammary / 1×10⁶ MC4-L2 s.c. in the flank	Forced treadmill running	-\|20–40min\|6–20 m/min\|15w	RTR: Sedentary before and after transplant RTE: EX after tumor transplant only ETR: EX before tumor transplant only ETE: EX before and after transplant 9w before tumor transplant, and/or 6w after transplant	- ETE had significantly slower growth compared to RTR - No difference in final tumor volume of RTE and ETR groups
Aveseh, 2015	68	5w old female Balb/c mice	Mammary / 1.2×10⁶ MC4-L2 cells in right dorsal mammary fat pad	Forced treadmill running	7×\|20–55min\|10–20 m/min\|7w	10d after tumor transplant	-EX decreased tumor volume
Malicka, 2015	45	4w old female Sprague Dawley rats	Mammary / 180 mg/kg MNU i.p.	Forced treadmill running	Low intensity (LIT): 5×\|10– 35min\|0.48–1.34 km/h\|12w Moderate intensity (MIT): 5×\|10– 35min\|0.6–1.68 km/h\|12w High intensity (HIT): 5×\|10– 35min\|0.72–2.0 km/h\|12w	Immediately after MNU injection	-No difference in final volume of total tumor volume
Piguet, 2015	46	7–9w old male AlbCrePten flox/flox mice	Hepatocellular carcinoma / Transgenic	Forced treadmill running	5w acclimation period followed by: 5×\|60m\|12.5m/min\|27w	7–9w of age	-EX decreased total volume of liver tumors
Hoffman, 1962	54	Wistar rats	Carcinoma / 2mL Walker 256 cell suspension s.c. into the right thigh.	Continuous running on a 20ft runway + swimming + revolving drum	21d of EX, all EX did all 3 modalities each day: Runway: continuous running on 20ft runway, duration and intensity not clear Swimming: increasing 20min/day to 4h/day Revolving drum: 5.4 mi in 12h	Immediately after injection	-97% inhibition of tumor growth. -Tumor weight ↓ in EX group
Gershbein, 1974	53	Holtzman rats	Carcinosarcoma / Walker-256 tumor i.m. into both hindlimbs.	Forced swimming	10×\|15min\|--\|10d	Immediately after injection.	-EX ↓ tumor size. -No change in survival rates.
Baracos, 1989	50	Sprague-Dawley rats	Hepatoma / 20uL Morris hepatoma 777 s.c.	Forced swimming	Low: 5×\|5min/d, increased by 5min/d for 3w. Medium: 5×\|10min/d, increased by 10min/d for 3w. High: 5×\|15min/d, increased by 15min/d for 3w.	2 Groups - 3w of swimming, tumor transplant, then 3w additional swimming. -3w of swimming beginning 3d post-transplant	-EX ↓ final tumor weight, both groups.
Radak, 2002	61	Adult female hybrid BDF1 mice	Solid leukemia / 5×10⁶ P-388 lymphoid leukemia cells s.c.	Forced swimming	5×\|60min\|--\|10w ET: training terminated at tumor implantation. EC: training continued for 18d after tumor implantation.	10w before injection.	-EC animals had slower tumor growth than ET and control, (endpoints were ~1.24cm³ vs. 2cm³ and 2.4cm³)
SáezMdel, 2007	34	50d old female Sprague-Dawley rats	Mammary / 5mg/w DMBA gastric intubation for 4w	Forced swimming	30m/d, 5d/w for 38–65d.	1d after appearance of first tumor	-EX ↑ tumor growth by 200%.
Almeida, 2009	47	7w old male Swiss mice	Carcinoma / 2×10⁶ Ehrlich tumor cells s.c. in the dorsum.	Forced swimming	5×\|60min\|50/80% max test\|6w. Progressive load test began after 1w: load increased by 2% BW every 3min until exhaustion.	4w before injection	-50% workload ↓ tumor weight and tumor volume (0.18mg/g and 0.11mm³) vs control (0.55mg/g and 0.48mm³) -Tumor volume and weight were 270% and 280% ↑ in SED mice.
Sasvari, 2011	62	Adult female BDF1 mice	Sarcoma / 5×10⁶ S- 180 cells s.c. injected.	Forced swimming	5×\|60m\|--\|10w ETT: cells injected after EX. ETC: EX (10w), cells injected, EX (18 additional days)	10w before tumor implantation.	-ETC ↓ final tumor weight vs. SED control.

EX = exercise or activity groups; SED = Sedentary controls; NMU = nitrosomethylurea; MNU= 1-methyl-1-nitrosourea; AOM= azoxymethane; DMBA= 7,12-dimethylbenz(a)anthracene; DMH= 1,2-dimethylhydrazine; 3’-Me-DAB= 3’-methyl-4-dimethylaminoazobenzene; Fe-NTA= ferric nitrilotriacetate; s.c.= sub-cutaneous; i.v.= intravenous